Methods for treating Huntington&#39;s disease

ABSTRACT

In particular, the present description relates to substituted monocyclic heteroaryl compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington&#39;s disease.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional of U.S. patent application Ser. No.15/781,303, filed on Jun. 4, 2018, which is the U.S. National Stagefiling under 35 U.S.C. § 371 of International Application No.PCT/US2016/066042, filed Dec. 11, 2016, which in turn claims priority toU.S. Provisional Application No. 62/265,652, filed Dec. 10, 2015, theentire contents of which are incorporated by reference herein.

The present description relates to compounds, forms, and pharmaceuticalcompositions thereof and methods of using such compounds, forms, orcompositions thereof for treating or ameliorating Huntington's disease.In particular, the present description relates to substituted monocyclicheteroaryl compounds, forms and pharmaceutical compositions thereof andmethods of using such compounds, forms, or compositions thereof fortreating or ameliorating Huntington's disease.

BACKGROUND

Huntington's disease (HD) is a progressive, autosomal dominantneurodegenerative disorder of the brain, having symptoms characterizedby involuntary movements, cognitive impairment, and mentaldeterioration. Death, typically caused by pneumonia or coronary arterydisease, usually occurs 13 to 15 years after the onset of symptoms. Theprevalence of HD is between three and seven individuals per 100,000 inpopulations of western European descent. In North America, an estimated30,000 people have HD, while an additional 200,000 people are at risk ofinheriting the disease from an affected parent. The disease is caused byan expansion of uninterrupted trinucleotide CAG repeats in the “mutant”huntingtin (Htt) gene, leading to production of HTT (Htt protein) withan expanded poly-glutamine (polyQ) stretch, also known as a “CAG repeat”sequence. There are no current small molecule therapies targeting theunderlying cause of the disease, leaving a high unmet need formedications that can be used for treating or ameliorating HD.Consequently, there remains a need to identify and provide smallmolecule compounds for treating or ameliorating HD.

All other documents referred to herein are incorporated by referenceinto the present application as though fully set forth herein.

SUMMARY

The present description relates to methods for treating or amelioratingHD in a subject in need thereof comprising administering to the subjectan effective amount of a compound of Formula (I):

wherein W, X, A and B are as defined herein, or forms and compositionsthereof.

In particular, the present description relates to a use of a compound ofFormula (I) or a form or composition thereof in a method for treating orameliorating HD in a subject in need thereof comprising, administeringan effective amount of the compound or a form or composition thereof, tothe subject.

The present description further relates to the use of a compound ofFormula (I) or a form thereof in combination with agents having additiveor synergistic activity, thus providing a combination product for thetreatment of HD.

DETAILED DESCRIPTION

The present description relates to a method or use of a compound fortreating or ameliorating HD in a subject in need thereof comprisingadministering to the subject an effective amount of a compound ofFormula (I):

-   or a form thereof, wherein-   W is CH═CH or S;-   X is CH₂, CH(C₁₋₄alkyl), C(C₁₋₄alkyl)₂, CH═CH, O, NR₅, or a bond;-   A is aryl, heteroaryl, heterocyclyl, or C₉₋₁₀cycloalkyl,-   wherein aryl is selected from phenyl and naphthyl, each optionally    substituted with 1, 2, 3, or 4 substituents each selected from R₁,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms, such as an O, S, or N atom,    each optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₁,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic, bicyclic or tricyclic ring system having 1, 2, or 3    heteroatom ring members independently selected from N, O, or S, each    optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₂, and-   wherein C₉₋₁₀cycloalkyl is a saturated or partially unsaturated    bicyclic ring system optionally substituted with 1, 2, 3, 4, or 5    substituents each selected from R₂;-   B is heterocyclyl,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic, bicyclic or polycyclic ring system having 1, 2, or 3    heteroatom ring members independently selected from N, O, or S, each    optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₄;-   R₁ is halogen, hydroxyl, cyano, C₁₋₄alkyl, halo-C₁₋₄alkyl, amino,    C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl,    C₁₋₄alkyl-amino-C₁₋₄alkyl, (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl,    amino-carbonyl, C₁₋₄alkyl-amino-carbonyl,    (C₁₋₄alkyl)₂-amino-carbonyl, C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, heterocyclyl-C₁₋₄alkoxy, phenyl, or    phenyl-C₁₋₄alkoxy,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms such as an O, S, or N atom,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring    members selected from N, O, and S, and-   wherein each instance of phenyl, heteroaryl or heterocyclyl is    optionally substituted with 1, or 2 substituents each selected from    R₃;-   R₂ is halogen, hydroxyl, cyano, oxo, hydroxyl-imino, C₁₋₄alkyl,    halo-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino,    amino-C₁₋₄alkyl, C₁₋₄alkyl-amino-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl, amino-carbonyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkoxy-carbonyl, C₂₋₄alkenyl, C₃₋₇cycloalkyl, or    heterocyclyl-C₁₋₄alkyl,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring    members selected from N, O, and S, and-   wherein each instance of heterocyclyl is optionally substituted with    1, or 2 substituents each selected from R₃;-   R₃ is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C₁₋₄alkyl,    halo-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino,    amino-C₁₋₄alkyl, C₁₋₄alkyl-amino-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl, amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl, (C₁₋₄alkyl)₂-amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, phenyl, or phenyl-C₁₋₄alkoxy;-   R₄ is independently selected from halogen, C₁₋₄alkyl,    hydroxyl-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino or    hydroxyl-C₁₋₄alkyl-amino; and-   R₅ is hydrogen, C₁₋₄alkyl, or hydroxyl-C₁₋₄alkyl;-   wherein a form of the compound is selected from the group consisting    of a prodrug, salt, hydrate, solvate, clathrate, isotopologue,    racemate, enantiomer, diastereomer, stereoisomer, polymorph and    tautomer form thereof.

An embodiment of the present description further relates to a method oruse of a compound for treating or ameliorating HD in a subject in needthereof comprising administering to the subject an effective amount of acompound of Formula (I) selected from a compound of Formula (Ia) andFormula (Ib):

-   or a form thereof, wherein-   X is CH₂, CH(C₁₋₄alkyl), C(C₁₋₄alkyl)₂, CH═CH, O, NR₅, or a bond;-   A is aryl, heteroaryl, heterocyclyl, or C₉₋₁₀cycloalkyl,-   wherein aryl is selected from phenyl and naphthyl, each optionally    substituted with 1, 2, 3, or 4 substituents each selected from R₁,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms, such as an O, S, or N atom,    each optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₁,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic, bicyclic or tricyclic ring system having 1, 2, or 3    heteroatom ring members independently selected from N, O, or S, each    optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₂, and-   wherein C₉₋₁₀cycloalkyl is a saturated or partially unsaturated    bicyclic ring system optionally substituted with 1, 2, 3, 4, or 5    substituents each selected from R₂;-   B is heterocyclyl,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic, bicyclic or polycyclic ring system having 1, 2, or 3    heteroatom ring members independently selected from N, O, or S, each    optionally substituted with 1, 2, 3, 4, or 5 substituents each    selected from R₄;-   R₁ is halogen, hydroxyl, cyano, C₁₋₄alkyl, halo-C₁₋₄alkyl, amino,    C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl,    C₁₋₄alkyl-amino-C₁₋₄alkyl, (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl,    amino-carbonyl, C₁₋₄alkyl-amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, heterocyclyl-C₁₋₄alkoxy, phenyl, or    phenyl-C₁₋₄alkoxy,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms such as an O, S, or N atom,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring    members selected from N, O, and S, and-   wherein each instance of phenyl, heteroaryl or heterocyclyl is    optionally substituted with 1, or 2 substituents each selected from    R₃;-   R₂ is halogen, hydroxyl, cyano, oxo, hydroxyl-imino, C₁₋₄alkyl,    halo-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino,    amino-C₁₋₄alkyl, amino-carbonyl, hydroxyl-C₁₋₄alkyl, C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₂₋₄alkenyl, C₃₋₇cycloalkyl, or    heterocyclyl-C₁₋₄alkyl;-   R₃ is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C₁₋₄alkyl,    amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl,    C₁₋₄alkyl-amino-C₁₋₄alkyl, (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl,    amino-carbonyl, C₁₋₄alkyl-amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, phenyl, or phenyl-C₁₋₄alkoxy;-   R₄ is independently selected from halogen, C₁₋₄alkyl,    hydroxyl-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino or    hydroxyl-C₁₋₄alkyl-amino; and-   R₅ is hydrogen, C₁₋₄alkyl, or hydroxyl-C₁₋₄alkyl;-   wherein a form of the compound is selected from the group consisting    of a prodrug, salt, hydrate, solvate, clathrate, isotopologue,    racemate, enantiomer, diastereomer, stereoisomer, polymorph and    tautomer form thereof.

Another embodiment of the present description further relates to methodsfor treating or ameliorating HD in a subject in need thereof comprisingadministering to the subject an effective amount of a compound ofFormula (I) selected from a compound of Formula (Ia) and Formula (Ib):

or a form thereof, whereinX is O, NH, N(CH₃) or a bond;A is aryl, heteroaryl or heterocyclyl,wherein aryl is selected from the group consisting of

wherein heteroaryl is selected from the group consisting of

wherein heterocyclyl is selected from the group consisting of

B is heterocyclyl selected from the group consisting of

-   R_(1a), R_(1b) and R_(1c) are each, where allowed by available    valences, one or more substituents each selected from halogen,    hydroxyl, cyano, C₁₋₄alkyl, halo-C₁₋₄alkyl, amino, C₁₋₄alkyl-amino,    (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl, C₁₋₄alkyl-amino-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl, amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl, (C₁₋₄alkyl)₂-amino-carbonyl,    C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, heterocyclyl-C₁₋₄alkoxy, phenyl, or    phenyl-C₁₋₄alkoxy,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms such as an O, S, or N atom,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring    members selected from N, O, and S, and-   wherein each instance of phenyl, heteroaryl or heterocyclyl is    optionally substituted with 1, or 2 substituents each selected from    R₃;-   R_(2a), R_(2b) and R_(2c) are each, where allowed by available    valences, one or more substituents each selected from halogen,    hydroxyl, cyano, oxo, hydroxyl-imino, C₁₋₄alkyl, halo-C₁₋₄alkyl,    amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl,    C₁₋₄alkyl-amino-C₁₋₄alkyl, (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl,    amino-carbonyl, hydroxyl-C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxy-carbonyl,    C₂₋₄alkenyl, C₃₋₇cycloalkyl, or heterocyclyl-C₁₋₄alkyl,-   wherein heterocyclyl is a saturated or partially unsaturated    monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring    members selected from N, O, and S, and-   wherein each instance of heterocyclyl is optionally substituted with    1, or 2 substituents each selected from R₃;-   R₃ is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C₁₋₄alkyl,    amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino, amino-C₁₋₄alkyl,    C₁₋₄alkyl-amino-C₁₋₄alkyl, (C₁₋₄alkyl)₂-amino-C₁₋₄alkyl,    amino-carbonyl, C₁₋₄alkyl-amino-carbonyl,    (C₁₋₄alkyl)₂-amino-carbonyl, C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    (C₁₋₄alkyl)₂-amino-carbonyl-C₁₋₄alkyl, C₁₋₄alkyl-carbonyl-amino,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    C₁₋₄alkyl-carbonyl, C₁₋₄alkoxy, halo-C₁₋₄alkoxy, amino-C₁₋₄alkoxy,    hydroxyl-C₁₋₄alkoxy, C₁₋₄alkyl-C₁₋₄alkoxy,    C₁₋₄alkyl-amino-C₁₋₄alkoxy, (C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy,    C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy, C₁₋₄alkoxy-C₁₋₄alkoxy,    C₁₋₄alkoxy-carbonyl, C₁₋₄alkoxy-carbonyl-amino,    C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy, C₂₋₄alkenyl,    C₂₋₄alkenyl-amino-carbonyl, C₃₋₇cycloalkyl,    C₃₋₇cycloalkyl-C₁₋₄alkoxy, C₃₋₇cycloalkenyl, heteroaryl,    heteroaryl-C₁₋₄alkyl, heteroaryl-C₁₋₄alkyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino,    heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl,    heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl, heterocyclyl,    heterocyclyl-C₁₋₄alkyl, phenyl, or phenyl-C₁₋₄alkoxy; and-   R_(4a), R_(4b), R_(4c), R_(4d), R_(4e), R_(4f) and R_(4g) are    independently selected from halogen, C₁₋₄alkyl, hydroxyl-C₁₋₄alkyl,    amino, C₁₋₄alkyl-amino, (C₁₋₄alkyl)₂-amino or    hydroxyl-C₁₋₄alkyl-amino;-   wherein a form of the compound is selected from the group consisting    of a prodrug, salt, hydrate, solvate, clathrate, isotopologue,    racemate, enantiomer, diastereomer, stereoisomer, polymorph and    tautomer form thereof.

Another aspect of the present description relates to a compound ofFormula (I) selected from a compound of Formula (Ia11), Formula (Ia15),Formula (Ia18) or Formula (Ib1):

-   or a form thereof, wherein (when present),-   X is selected from O, NR₅, or a bond;-   A is selected from phenyl, thiophenyl, indazolyl, pyridinyl,    pyrimidinyl or phenoxy,-   wherein phenyl and phenoxy are each optionally substituted with 1, 2    or 3 substituents each selected from R_(1a),-   wherein thiophenyl, indazolyl, pyridinyl, pyrimidinyl are each    optionally substituted with 1 or 2 substituents each selected from    R_(1a),-   B is selected from 1H-pyrazolyl, piperidinyl,    1,2,3,6-tetrahydropyridinyl, (1R,5S)-8-azabicyclo[3.2.1]octyl,    8-azabicyclo[3.2.1]oct-2-enyl, 2,6-diazaspiro[3.4]octyl or    2,7-diazaspiro[3.5]nonyl, each optionally substituted with 1 or 2    substituents each selected from R_(4a);-   R_(1a) is selected from halogen, hydroxyl, C₁₋₄alkyl,    halo-C₁₋₄alkyl, amino, C₁₋₄alkoxy, or heteroaryl,-   wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic    carbon atom ring structure radical in which one or more carbon atom    ring members have been replaced, where allowed by structural    stability, with one or more heteroatoms such as an O, S, or N atom,    optionally substituted with 1 or 2 substituents each selected from    R_(3a);-   R_(3a) is selected from nitro or C₁₋₄alkyl; and,-   R_(4a) is C₁₋₄alkyl;-   R_(5a) is hydrogen, C₁₋₄alkyl, or hydroxyl-C₁₋₄alkyl;-   wherein a form of the compound is selected from the group consisting    of a prodrug, salt, hydrate, solvate, clathrate, isotopologue,    racemate, enantiomer, diastereomer, stereoisomer, polymorph and    tautomer form thereof.

Another aspect of the present description relates to a compound ofFormula (I) selected from a compound of Formula (Ia11), Formula (Ia15),Formula (Ia18) or Formula (Ib1):

-   or a form thereof, wherein (when present),-   R_(1a) is selected from fluoro, chloro, hydroxyl, methyl,    difluoromethyl, amino, methoxy or 1H-pyrazolyl or 1H-imidazol-1-yl,-   wherein 1H-pyrazolyl is optionally substituted with 1 or 2    substituents each selected from R_(3a);-   R_(3a) is selected from nitro or methyl or amino; and,-   R_(4a) is methyl or ethyl;-   R_(5a) is hydrogen or methyl;-   wherein a form of the compound is selected from the group consisting    of a prodrug, salt, hydrate, solvate, clathrate, isotopologue,    racemate, enantiomer, diastereomer, stereoisomer, polymorph and    tautomer form thereof.

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia1) or a form thereof, wherein substituentsR_(1a), R_(1b), and X, when present, are indicated in the table belowwith multiple substituents separated by a comma; and, “--” indicatesthat one or more R_(1a), R_(1b), and X substituents are not present:

(Ia1)

Cpd R_(1a) R_(1b) X   1 — — NH   8 2-OH — N(CH₃)  40 1-CH₂CH═CH₂, —N(CH₃) 2-OH 106 1-Br, 7-OH N(CH₃) 2-OH 107 1-Cl, 7-OH N(CH₃) 2-OH

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia2) or a form thereof, wherein substituentsR_(1a), R_(1b), and R_(4a), when present, are indicated in the tablebelow with multiple substituents separated by a comma; and, “--”indicates that one or more R_(1a), R_(1b), and R_(4a) substituents arenot present:

(Ia2)

Cpd R_(1a) R_(1b) R_(4a)  13 — — — 207 — 7-OH — 208 — 7-OH CH₃ 210 2-CH₃7-OH — 222 3-Cl 7-OH — 223 3-Br 7-OH — 224 3-CN 7-OH — 2253-(1-CH₃-1H-imidazol-4-yl) 7-OH — 226 3-(1H-imidazol-1-yl) 7-OH — 2273-OH 7-OH — 228 3-CH₂CH₃ 7-OH — 229 3-CH(CH₃)₂ 7-OH — 232 2-CH₃, 7-OH —4-OCH₃, 233 2-CH₃, 7-OH — 4-(pyrrolidin-1-yl) 234 2-CH₃, 7-OH —4-(morpholin-4-yl) 235 2-CH₃, 7-OH — 4-N(CH₃)₂ 236 2-CH₃, 7-OH —4-OCH₂CH₃ 237 2-CH₃, 7-OH — 4-(1-CH₃-1H-pyrazol-4-yl) 2403-(tetrahydro-2H-pyran-4-yl) 7-OH — 249 4-OCH₃ 7-OH — 250 2-CH₃, 7-OH —4-(azetidin-1-yl) 251 2-CH₃, 7-OH — 4-CN 252 2-CH₃, 7-OH — 4-cyclopropyl253 2-CH₃, 7-OH — 4-(3,6-dihydro-2H-pyran-4-yl) 254 2-CH₃, 7-OH —4-(tetrahydro-2H-pyran-4-yl) 255 2-CH₃, 7-OH — 4-(oxetan-3-yl) 2564-N(CH₃)₂ 7-OH — 262 2-CN 7-OH — 265 2-C(O)NH₂ 7-OH — 293 3-Cl 7-OH —294 3-CH(CH₃)₂ 7-OH — 296 2-CH₃, 7-OH — 4-Cl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia3) or a form thereof, wherein substituentsR_(1a), R_(1b) and X, when present, are indicated in the table belowwith multiple substituents separated by a comma; and, “--” indicatesthat one or more R_(1a), R_(1b) and X substituents are not present:

Cpd R_(1a) R_(1b) X 11 — — O 15 — — N(CH₃) 218 — 7-OH N(CH₃) 261 1-CN7-OH N(CH₃) 272 1-CH₃ 7-OH N(CH₃) 275 1-CN, 3-CH₃ 7-OH N(CH₃) 2923-(OCH₂-phenyl) — N(CH₃)

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia4) or a form thereof, wherein substituents X,R_(1a), R_(1b) and R_(4a), when present, are indicated in the tablebelow; and, “--” indicates that one or more X, R_(1a), R_(1b) and R_(4a)substituents are not present:

Cpd R_(1a) R_(1b) X R_(4a) 10 — — O — 14 — — N(CH₃) — 1591-(OCH₂-phenyl) — N(CH₃) — 211 — 6-OH N(CH₃) CH₃ 212 — 6-OH N(CH₃) — 213— 6-OH O — 215 1-cyclopropyl 6-OH N(CH₃) — 216 1-OH 6-OH N(CH₃) — 2171-CN 6-OH N(CH₃) — 264 1-C(O)NH₂ 6-OH N(CH₃) — 273 1-CH₃ 6-OH N(CH₃) —274 1,3-(CH₃)₂ 6-OH N(CH₃) — 276 1-NH₂ 6-OH N(CH₃) — 283 1-OCH₂CH₃ 6-OHN(CH₃) — 284 1-OH 6-OH O — 285 3-phenyl 6-OH N(CH₃) — 286 3-CH₃ 6-OHN(CH₃) — 287 3-cyclopropyl 6-OH N(CH₃) — 288 3-CH(CH₃)₂ 6-OH N(CH₃) —289 3-(CH₂)₂CH₃ 6-OH N(CH₃) — 290 3-CH(CH₃)₂ 6-OH O

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia5) or a form thereof, wherein substituents R_(1a)and R_(1b), when present, are indicated in the table below with multiplesubstituents separated by a comma; and, “--” indicates that one or moreR_(1a) and R_(1b) substituents are not present:

Cpd R_(1a) R_(1b) 12 — — 220 — 6-OH 221 2-CH₃ 6-OH 238 4-OCH₃ 6-OH 2413-Cl 6-OH 242 3-Br 6-OH 243 3-CH₃ 6-OH 244 3-CH₃ 5-Br, 6-OH 263 2-CN6-OH 266 2-C(O)NH₂ 6-OH 267 2-CO₂CH₃ 6-OH 297 4-Cl 6-OH 300 — 6-OH

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia6) or a form thereof, wherein substituentsR_(1a), when present, are indicated in the table below; and, “--”indicates that one or more R_(1a) substituents are not present:

Cpd R_(1a) 239 — 246 2,3-(CH₃)₂ 247 2-CH₃ 248 3-CH₃

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia7) or a form thereof, wherein substituentsR_(1a), when present, are indicated in the table below; and, “--”indicates that one or more R_(1a) substituents are not present:

Cpd R_(1a) 258 — 260 2-CH₃

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia8) or a form thereof, wherein substituents R_(1a)and B, when present, are indicated in the table below; and, “--”indicates that one or more R_(1a) and B substituents are not present:

Cpd R_(1a) B 209 —6-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl) 269 2-CNpiperazin-1-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia9) or a form thereof, wherein substituents R_(1a)and B, when present, are indicated in the table below; and, “--”indicates that one or more R_(1a) and B substituents are not present:

Cpd R_(1a) B 214 —6-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl) 270 —piperazin-1-yl 291 3-CH₃ piperazin-1-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia10) or a form thereof, wherein substituentsR_(1a) and B, when present, are indicated in the table below; and, “--”indicates that one or more R_(1a) and B substituents are not present:

Cpd R_(1a) B 268 2-CN piperazin-1-yl 271 —1,2,3,6-tetrahydropyridin-4-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia11) or a form thereof, wherein substituents A, Xand R_(4a), when present, are indicated in the table below; and, “--”indicates that one or more A, X and R_(4a) substituents are not present:

Cpd A X R_(4a) 2 benzo[b]thiophen-2-yl N(CH₃) — 45-CN-benzo[b]thiophen-2-yl N(CH₃) — 5 quinolin-3-yl NH — 6benzo[b]thiophen-2-yl O — 9 benzo[b]thiophen-2-yl NH — 16imidazo[1,2-a]pyridin-6-yl N(CH₃) — 17 6-phenyl-pyridin-3-yl N(CH₃) — 186-(1H-pyrrol-1-yl)-pyridin-3-yl N(CH₃) — 196-(1H-pyrazol-1-yl)-pyridin-3-yl N(CH₃) — 20 quinoxalin-2-yl N(CH₃) — 21quinolin-3-yl N(CH₃) — 22 phthalazin-6-yl N(CH₃) — 23benzo[c][1,2,5]oxadiazol-5-yl NH — 24 benzo[d]thiazol-5-yl NH — 252-CH₃-benzo[d]oxazol-6-yl NH — 30 2-(4-CN-phenol) N(CH₃) — 322-(4-CF₃-phenol) N(CH₃) — 33 6-(2-F-phenol) N(CH₃) — 342-[3,5-(OCH₃)₂-phenol] N(CH₃) — 35 2-[4,5-(OCH₃)₂-phenol] N(CH₃) — 372-(4,5-F₂-phenol) N(CH₃) — 41 benzo[b]thiophen-2-yl NH CH₃ 532-[4-(1H-pyrazol-1-yl)-phenol] N(CH₃) — 1152-[3-OH-5-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1162-[3-OCH₃-5-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1172-[5-(1H-pyrazol-4-yl)-3-OCF₃-phenol] NH — 1182-[5-(1-CH₃-1H-pyrazol-4-yl)-3-OCF₃-phenol] N(CH₃) — 1192-[5-(1H-pyrazol-4-yl)-3-OCF₃-phenol] N(CH₃) — 1202-[5-(1-CH₃-pyridin-2(1H)-one)-3-OCF₃-phenol] N(CH₃) — 1212-[3-OCH₃-5-(1-CH₃-1H-pyrazol-4-yl)-phenol] N(CH₃) — 1222-[3-OCH₃-5-(5,6,7,8-tetrahydroimidazo-[1,2- a]pyridin-3-yl)-phenol]N(CH₃) — 123 2-[3-OCH₃-5-(pyridin-3-yl)-phenol] N(CH₃) 1242-[3-OCH₃-5-(1-cyclopentyl-1H-pyrazol-4- yl)-phenol] N(CH₃) 1252-[5-(3-OCH₃-phenyl)-3-OCH₃-phenol] N(CH₃) 1262-[3-benzyloxy-5-(5-CH₃-oxazol-2-yl)-phenol] N(CH₃) 1272-[3-OCH₂CH₃-5-(5-CH₃-oxazol-2-yl)-phenol] N(CH₃) — 1282-[3-(OCH₂-cyclopropyl)-5-(5-CH₃-oxazol-2-yl)- phenol] N(CH₃) — 1295-(2-CH₃-1H-benzo[d]imidazol-6-ol) N(CH₃) — 1342-[4-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1352-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3- yl)-phenol] N(CH₃) —136 2-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3- yl)-phenol] N(CH₃)— 137 2-[4-(1H-indol-2-yl)-phenol] N(CH₃) — 1382-[4-(cyclopent-1-en-1-yl)-phenol] N(CH₃) — 1392-[4-(1H-pyrazol-3-yl)-phenol] N(CH₃) — 1402-[4-(2-OH-pyridin-4-yl)-phenol] N(CH₃) — 1412[4-(1-CH₃-pyridin-2(1H)-one)-phenol] O — 1422-[4-(2-OH-pyridin-4-yl)-phenol] O — 1442-[4-Cl-5-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1452-[4-F-5-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1462-[5-F-4-(1H-imidazol-4-yl)-phenol] N(CH₃) — 1472-[5-F-4-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1482-[5-F-(1H-pyrazol-5-yl)-phenol] N(CH₃) — 1496-OH-1-oxo-2,3-dihydro-1H-inden-5-yl N(CH₃) — 1506-(1,4-dihydroindeno[1,2-c]-1H-pyrazol-7-ol) N(CH₃) — 1516-OH-1-OH-imino-2,3-dihydro-1H-inden-5-yl N(CH₃) — 1526-OH-1-OH-2,3-dihydro-1H-inden-5-yl N(CH₃) — 1536-(2-NH₂-8H-indeno[1,2-d]thiazol-5-ol) N(CH₃) 1549-(5,6-dihydroimidazo[5,1-a]isoquinolin-8-ol) N(CH₃) — 1552-{4-[C(O)NHCH₂-(1-CH₃-1H-pyrazol- 4-yl)]phenol} (CH₃) — 1562-[4-(4-CH₂OH-1H-pyrazol-1-yl)-phenol] N(CH₃) — 1583-(OCH₂-phenyl)-isoquinolin-6-yl N(CH₃) — 1602-[3-F-5-(2-OCH₃-pyridin-4-yl)-phenol] N(CH₃) — 1614-[1-(4-pyridin-2(1H)-one)-3-F-5-OH-phenyl] N(CH₃) — 1624-{1-[4-(1-CH₃-pyridin-2(1H)-one)]-3-F-5- OH-phenyl} N(CH₃) — 1634-{1-[5-(1-CH₃-pyridin-2(1H)-one)]-3-F-5- OH-phenyl} N(CH₃) — 1642-[3-F-5-(1H-pyrazol-4-yl)-phenol] O — 165 2-(5-Cl-3-F-phenol) N(CH₃) —166 2-[3-F-5-(1H-pyrazol-4-yl)-phenol] N(CH₃) — 1672-[3-F-5-(1-CH₃-1H-pyrazol-4-yl)-phenol] N(CH₃) — 219 8-(quinolin-7-ol)N(CH₃) — 230 6-(7-OH-quinolin-2(1H)-one) N(CH₃) — 2316-(7-OH-1-CH₃-quinolin-2(1H)-one) N(CH₃) — 2457-(6-OH-1-CH₃-quinolin-4(1H)-one) N(CH₃) — 2576-(7-OH-quinazolin-4(1H)-one) N(CH₃) — 2596-(7-OH-1-CH₃-3,4-dihydroquinolin-2(1H)-one) N(CH₃) — 2777-OH-1,3-(CH₃)2-quinazolin-6-yl-2,4(1H,3H)- dione N(CH₃) — 2786-OH-benzo[d]oxazol-5-yl-2(3H)-one N(CH₃) — 2792-CH₃-6-OH-2H-indazol-5-yl N(CH₃) — 280 1-CH₃-6-OH-1H-indazol-5-ylN(CH₃) — 281 7-(6-OH-2-CH₃-isoquinolin-1(2H)-one) N(CH₃) — 2827-(6-OH-2-CH₂CH₃-isoquinolin-1(2H)-one) O —

Another embodiment of the present description includes a compound ofFormula (Ia) or a form thereof selected from a compound of Formula(Ia11) or a form thereof, wherein substituents A, X and R_(4a), whenpresent, are indicated in the table below; and, “--” indicates that oneor more A, X and R_(4a) substituents are not present:

Cpd A X 420 2-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl N(CH₃) 4282,5-F₂-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4302,3-F₂-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4312,5-F₂-4-(1H-pyrazol-4-yl)phenyl O 434 2-OCH₃-4-(1H-pyrazol-4-yl)phenylN(CH₃) 435 4-(1H-pyrazol-4-yl)phenyl O 437 2-F-4-(1H-pyrazol-4-yl)phenylO 438 4-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl O 440 2-F-4-OH-phenylN(CH₃) 442 2-CH₃-2H-indazol-5-yl N(CH₃) 443 2-CH₃-2H-indazol-5-yl O 4444-Cl-2-OCH₃-phenyl O 445 2-CH₃-pyrazolo[1,5-a]pyridin-3-yl N(CH₃) 446imidazo[1,2-a]pyridin-6-yl O 447 2-OCH₃-4-(1H-pyrazol-1-yl)phenyl O 4485-(1H-pyrazol-4-yl)thiophen-2-yl O 4495-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl O 4504-(1H-pyrazol-4-yl)thiophen-2-yl O 4512-OH-4-[3,5-(CH₃)₂-1H-pyrazol-4-yl]phenyl O 4522-F-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 453 2-OCH₃-4-OH-phenyl O 4542-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl O 455 2,4-(OH)₂-phenyl O 4562-Cl-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4575-amino-2-(1H-pyrazol-4-yl)pyrimidin-4-yl O 4582,6-F₂-4-(1H-pyrazol-4-yl)phenyl O 4642-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl O 4652-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl N(CH₃)

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia11) or a form thereof, wherein substituents A, Xand R_(4a), when present, are indicated in the table below; and, “--”indicates that one or more A, X and R_(4a) substituents are not present:

Cpd A X 420 2-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl N(CH₃) 4282,5-F₂-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4302,3-F₂-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4312,5-F₂-4-(1H-pyrazol-4-yl)phenyl O 434 2-OCH₃-4-(1H-pyrazol-4-yl)phenylN(CH₃) 435 4-(1H-pyrazol-4-yl)phenyl O 437 2-F-4-(1H-pyrazol-4-yl)phenylO 438 4-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl O 440 2-F-4-OH-phenylN(CH₃) 442 2-CH₃-2H-indazol-5-yl N(CH₃) 443 2-CH₃-2H-indazol-5-yl O 4444-Cl-2-OCH₃-phenyl O 445 2-CH₃-pyrazolo[1,5-a]pyridin-3-yl N(CH₃) 446imidazo[1,2-a]pyridin-6-yl O 447 2-OCH₃-4-(1H-pyrazol-1-yl)phenyl O 4485-(1H-pyrazol-4-yl)thiophen-2-yl O 4495-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl O 4504-(1H-pyrazol-4-yl)thiophen-2-yl O 451 2-OH-4-[3,5-(CH₃)₂-1H-pyrazol-4-yl]phenyl O 452 2-F-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4532-OCH₃-4-OH-phenyl O 454 2-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl O 4552,4-(OH)₂-phenyl O 456 2-Cl-4-(1H-pyrazol-4-yl)phenyl N(CH₃) 4575-amino-2-(1H-pyrazol-4-yl)pyrimidin-4-yl O 4582,6-F₂-4-(1H-pyrazol-4-yl)phenyl O 4642-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl O 4652-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl N(CH₃)

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia12) or a form thereof, wherein substituents X,R_(1a) and B, when present, are indicated in the table below; and, “--”indicates that one or more X, R_(1a) and B substituents are not present:

Cpd R_(1a) X B 66 H NH azetidin-3-yl 82 OH — piperazin-1-yl 85 H —1,2,3,6-tetrahydropyridin-4-yl 86 OH — 1,2,3,6-tetrahydropyridin-4-yl 87OH — 2,2,6,6-tetramethyl-(1,2,3,6- tetrahydropyridin-4-yl) 88 OH —1-CH₃-(1,2,3,6-tetrahydropyridin-4-yl) 89 OH — piperidin-4-yl 99 H CH₂piperidin-4-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia13) or a form thereof, wherein substituents X,R_(1a) and R_(4a), when present, are indicated in the table below; and,“--” indicates that one or more X, R_(1a) and R_(4a) substituents arenot present:

Cpd X R_(1a) R_(4a) 26 N(CH₃) H — 28 NH H — 31 O H — 90 O OH — 91 N(CH₃)OH — 92 NH OH — 93 N(CH₃) O(CH₂)₃NHCO₂C(CH₃)₃ — 94 N(CH₃) O(CH₂)₃NH₂ —95 N(CH₃) O(CH₂)₃NHCO₂CH₃ — 96 N(CH₃) O(CH₂)₃OH — 97 N(CH₃) O(CH₂)₃OCH₃— 98 O O(CH₂)₃-morpholin-4-yl — 103 N(CH₃) CN — 104 N(CH₃)CH₂-1-piperidinyl — 105 N(CH₃) CH₂-pyrrolidin-1-yl — 108 N(CH₃) OCH₃ —109 N(CH₃) OCH₃ CH₃ 110 N(CH₃) 3,6-dihydro-2H-pyran-4-yl — 111 N(CH₃)tetrahydro-2H-pyran-4-yl — 112 N(CH₃) CHF₂ — 113 N(CH₃) OC(CH₃)₂(CH₂)₂OH— 114 N(CH₃) O(CH₂)₂C(CH₃)₂OH —

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia14) or a form thereof, wherein substituents X andB, when present, are indicated in the table below; and, “--” indicatesthat one or more X and B substituents are not present:

Cpd X B 55 O piperidin-4-yl 56 O (2S,4R,6R)-2,6-(CH₃)₂-piperidin-4-yl 57O 2,6-(CH₃)₂-piperidin-4-yl 58 O pyrrolidin-3-yl 59 O2-CH₃-piperidin-4-yl 60 OCH₂ 1H-pyrrolidin-3-yl 61 O 3-F-piperidin-4-yl65 — piperazin-1-yl 67 NH azetidin-3-yl 68 — 3,5-(CH₃)₂-piperazin-1-yl69 — 7-CH₃-2,7-diazaspiro[4.4]non-2-yl 70 — [1,4]diazepan-1-yl 71 —4-CH₂CH₂OH-piperazin-1-yl 72 — 2,7-diazaspiro[3.5]non-7-yl 73 —2,7-diazaspiro[3.5]non-7-yl 74 — 3-CH₂OH-piperazin-1-yl 75 —1,7-diazaspiro[4.4]non-7-yl 76 — 4-NH₂-4-CH₃-piperidin-1-yl 77 —3-N(CH₃)₂-piperidin-1-yl 79 — 3,3-(CH₃)₂-piperazin-1-yl 80 —7-CH₂CH₂OH-2,7-diazaspiro[4.4]-nonan-2-yl 83 —1,2,3,6-tetrahydropyridin-4-yl 84 — piperidin-4-yl 102 O(6S)-6-[(S)-CH(OH)CH₃]-2,2-(CH₃)₂-piperidin-4-yl 133 O2,2-(CH₃)₂-piperidin-4-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia15) or a form thereof, wherein substituents X,R_(1a) and R_(4a), when present, are indicated in the table below; and,“--” indicates that one or more X, R_(1a) and R_(4a) substituents arenot present:

Cpd X R_(1a) R_(4a) 3 NH H — 7 N(CH₃) H — 27 N(CH₃) Cl CH₃ 29 NH Cl CH₃36 N(CH₃) OCH₃ — 38 N(CH₃) F — 39 N(CH₃) CN — 42 N(CH₃) C(O)NHCH₂CH═CH₂— 43 N(CH₃) 1H-pyrazol-1-yl — 44 N(CH₃) 5-CH₃-oxazol-2-yl — 45 N(CH₃)4-CH₂OH-1H-pyrazole-1-yl — 46 N(CH₃) 1H-imidazole-1-yl — 47 N(CH₃)4-NH₂-1H-pyrazol-1-yl — 48 N(CH₃) 1H-pyrazol-4-yl — 49 N(CH₃)3-NH₂-1H-pyrazol-1-yl — 50 N(CH₃)1-(CH₂CH₂-morpholin-4-yl)-1H-pyrazol-4-yl — 51 N(CH₃)1-CH₃-1H-pyrazol-4-yl — 52 N(CH₃) 5-NH₂-1H-pyrazol-1-yl — 54 N(CH₂CH₂OH)1H-pyrazol-1-yl — 62 O 1H-pyrazol-1-yl CH₃ 63 O 1H-pyrazol-1-yl — 64 O1H-pyrazol-4-yl — 78 NH 1H-pyrazol-1-yl CH₃ 100 CH₂ 1H-pyrazol-1-yl —130 N(CH₃) Cl — 131 NH 1H-pyrazol-1-yl — 132 NH CN — 143 N(CH₃)1H-indazol-7-yl — 157 CH₂ 1H-pyrazol-4-yl — 168 N(CH₃)5-OCH₃-pyridin-3-yl — 169 N(CH₃) 5-pyridin-2-ol — 170 N(CH₃)4-pyridin-2-ol — 171 N(CH₃) 6-OCH₃-pyridin-3-yl — 172 N(CH₃)5-(3-CF₃-pyridin-2-ol) — 173 N(CH₃) 5-(1-CH₃-pyridin-2(1H)-one) — 174N(CH₃) 4-(1-CH₃-pyridin-2(1H)-one) — 175 N(CH₃) 2-OCH₃-pyridin-4-yl —176 O 4-pyridin-2-ol — 177 N(CH₃) 6-N(CH₃)₂-pyridin-3-yl — 178 O4-(1-CH₃-pyridin-2(1H)-one) — 179 N(CH₃) pyrimidin-5-yl — 180 N(CH₃)5-pyridin-3-ol — 181 N(CH₃) 4-(1-cyclopropyl-pyridin-2(1H)-one) — 182N(CH₃) 1,2,3,6-tetrahydropyridin-4-yl — 183 N(CH₃) cyclopent-1-en-1-yl —184 N(CH₃) 3,6-dihydro-2H-pyran-4-yl — 185 N(CH₃)imidazo[1,5-a]pyridin-7-yl — 186 N(CH₃) imidazo[1,2-a]pyridin-7-yl — 187N(CH₃) 2-CH₃-pyridin-4-yl — 188 N(CH₃) 1H-imidazol-2-yl — 189 N(CH₃)1H-imidazol-4-yl — 190 N(CH₃) imidazo[1,2-a]pyrazin-3-yl — 191 N(CH₃)5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl — 192 N(CH₃)4-CH₃-1H-imidazol-2-yl — 193 N(CH₃) 1-CH₃-1H-imidazol-4-yl — 194 N(CH₃)1-CH₃-1H-imidazol-5-yl — 195 N(CH₃) 4-NO₂-1H-imidazol-2-yl — 196 N(CH₃)2-CH₃-1H-imidazol-4-yl — 197 N(CH₃) 1,2-(CH₃)₂-1H-imidazol-4-yl — 198N(CH₃) 4-C(O)NH₂-1H-pyrazol-1-yl — 206 N(CH₃) H —

Another embodiment of the present description includes a compound ofFormula (Ia) or a form thereof selected from a compound of Formula(Ia15) or a form thereof, wherein substituents X, R_(1a) and R_(4a),when present, are indicated in the table below; and, “--” indicates thatone or more X, R_(1a) and R_(4a) substituents are not present:

(Ia15)

Cpd X R_(1a) R_(4a) 413 NH 1H-pyrazol-4-yl — 414 O 1-CH₃-1H-pyrazol-4-yl— 416 N(CH₃) 5-CH₃-1H-pyrazol-4-yl — 417 O 1H-imidazol-1-yl — 418 O5-CH₃-1H-pyrazol-4-yl — 419 N(CH₃) 4-NO₂-1H-pyrazol-1-yl — 421 O4-NH₂-1H-pyrazol-1-yl — 423 O 4-NO₂-1H-pyrazol-1-yl — 460 N(CH₃)1H-pyrazol-4-yl — 461 O 1H-pyrazol-4-yl —

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia15) or a form thereof, wherein substituents X,R_(1a) and R_(4a), when present, are indicated in the table below; and,“--” indicates that one or more X, R_(1a) and R_(4a) substituents arenot present:

(Ia15)

Cpd X R_(1a) 413 NH 1H-pyrazol-4-yl 414 O 1-CH₃-1H-pyrazol-4-yl 416N(CH₃) 5-CH₃-1H-pyrazol-4-yl 417 O 1H-imidazol-1-yl 418 O5-CH₃-1H-pyrazol-4-yl 419 N(CH₃) 4-NO₂-1H-pyrazol-1-yl 421 O4-NH₂-1H-pyrazol-1-yl 423 O 4-NO₂-1H-pyrazol-1-yl 460 N(CH₃)1H-pyrazol-4-yl 461 O 1H-pyrazol-4-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia16) or a form thereof, wherein substituentsR_(1a) and R_(4a), when present, are indicated in the table below; and,“--” indicates that one or more R_(1a) and R_(4a) substituents are notpresent:

(Ia16)

Cpd R_(1a) R_(4a)  81 1H-pyrazol-1-yl — 199 1H-pyrazol-4-yl (CH₂)₂OH 2001H-pyrazol-4-yl — 201 1H-pyrazol-4-yl CH₃ 2024-(1-CH₃-pyridin-2(1H)-one) CH₃ 203 4-(1-CH₃-pyridin-2(1H)-one) CH₃

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia17) or a form thereof, wherein substituentR_(1a), when present, is indicated in the table below; and, indicatesthat one or more R_(1a) substituents are not present:

(Ia17)

Cpd R_(1a) 204 1H-pyrazol-4-yl 205 4-(1-CH₃-pyridin-2(1H)-one)

Another embodiment of the present description includes a compound ofFormula (Ia) or a form thereof selected from a compound of Formula(Ia18) or a form thereof, wherein substituents X and B, when present,are indicated in the table below; and, “--” indicates that one or more Xand B substituents are not present:

(Ia18)

Cpd X B 411 N(CH₃) (1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 412 NH(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 415 O(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 422 —1-CH₃-(1,2,3,6-tetrahydropyridin-4-yl) 424 —1,2,3,6-tetrahydropyridin-4-yl 425 —1-CH₃CH₂-(1,2,3,6-tetrahydropyridin-4-yl) 426 N(CH₃) piperidin-4-yl 427NH piperidin-4-yl 429 — 8-azabicyclo[3.2.1]oct-2-en-3-yl 432 Opiperidin-4-yl 433 NH (1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 436 O2,6-(CH₃)₂-piperidin-4-yl 439 — 2,7-diazaspiro[3.5]non-2-yl 441 O2,6-(CH₃)₂-piperidin-4-yl 459 — 2,6-diazaspiro[3.4]oct-2-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ia) or a form thereof selected from acompound of Formula (Ia18) or a form thereof, wherein substituents X,R_(1a) and B, when present, are indicated in the table below; and, “--”indicates that one or more X, R_(1a) and B substituents are not present:

(Ia18)

Cpd X B 411 N(CH₃) (1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 412 NH(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 415 O(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 422 —1-CH₃-(1,2,3,6-tetrahydropyridin-4-yl) 424 —1,2,3,6-tetrahydropyridin-4-yl 425 —1-CH₃CH₂-(1,2,3,6-tetrahydropyridin-4-yl) 426 N(CH₃) piperidin-4-yl 427NH piperidin-4-yl 429 — 8-azabicyclo[3.2.1]oct-2-en-3-yl 432 Opiperidin-4-yl 433 NH (1R,5S)-8-azabicyclo[3.2.1]oct-3-yl 436 O2,6-(CH₃)₂-piperidin-4-yl 439 — 2,7-diazaspiro[3.5]non-2-yl 441 O2,6-(CH₃)₂-piperidin-4-yl 459 — 2,6-diazaspiro[3.4]oct-2-yl

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib1) or a form thereof, wherein substituent A isindicated in the table below:

(Ib1)

Cpd A 302 6-(naphthalen-2-ol) 320 6-(naphthalen-2,7-diol) 3317-OCH₃-quinolin-6-yl 332 7-OH-quinolin-6-yl 3372-CN-7-OCH₃-quinolin-6-yl 355 3-F-5-(1H-pyrazol-4-yl)-pyridin-2-yl 3642-(6-OCH₃-3,4-dihydroisoquinolin-1(2H)-one) 3926-OH-1-oxo-2,3-dihydro-1H-inden-5-yl 4013-(4-OCH₃-1-CH₃-quinolin-2(1H)-one) 4023-(4-OH-1-CH₃-quinolin-2(1H)-one) 403 3-(quinolin-2(1H)-one) 4043-(1-OCH₃-quinolin-2(1H)-one) 408 5-CN-benzo[b]thiophen-2-yl 4093-Cl-benzo[b]thiophen-2-yl

Another embodiment of the present description includes a compound ofFormula (Ib) or a form thereof selected from a compound of Formula (Ib1)or a form thereof, wherein substituent A is indicated in the tablebelow:

Cpd A 462 3-(1H-pyrazol-4-yl)phenoxy 463 4-(1H-pyrazol-4-yl)phenoxy

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib1) or a form thereof, wherein substituent A isindicated in the table below:

(Ib1)

Cpd A 462 3-(1H-pyrazol-4-yl)phenoxy 463 4-(1H-pyrazol-4-yl)phenoxy

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib2) or a form thereof, wherein substituent A isindicated in the table below:

(Ib2)

Cpd A 321 6-naphthalen-2,7-diol

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib3) or a form thereof, wherein substituentsR_(1a), R_(1b) and B, when present, are indicated in the table below;and, “--” indicates that one or more R_(1a), R_(1b) and B substituentsare not present:

(Ib3)

Cpd R_(1a) R_(1b) B 329 1H-pyrazol-1-yl OCH₃1,2,3,6-tetrahydropyridin-4-yl 330 1H-pyrazol- 1-yl OH piperazin-l-yl381 1H-pyrazol-1-yl Cl 5-((3aR,6aR)-1-CH₃- hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl) 382 1H-pyrazol-1-yl Cl 2-NHCH(CH₃)2-morpholin-4-yl383 1H-pyrazol-1-yl Cl 2-OCH₃-2,7- diazaspiro[4.5]decan-7-yl 3851-CH₃-1H- OCH₃ 5-((3aR,6aS)-5-CH₃- pyrazol-4-yl hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl) 394 1-CH₃-1H- OH 5-((3aR,6aS)-5-CH₃- pyrazol-4-ylhexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl) 406 1H-pyrazol-1-yl Cl2,7-diazaspiro [4.5] decan-2-yl 407 1H-pyrazol-1-yl Cl(3R)-(3-(R)-CH₂OH)- piperazin-1-yl

Another embodiment of the ccpresent description includes the use of acompound of Formula (Ib) or a form thereof selected from a compound ofFormula (Ib4) or a form thereof, wherein substituents R_(1a), R_(1b),R_(1c), R_(1d) (each representative of the scope of R₁) and X, whenpresent, are indicated in the table below; and, “--” indicates that oneor more R_(1a), R_(1b), R_(1c), R_(1d) and X substituents are notpresent:

(Ib4)

Cpd R_(1a) R_(1b) R_(1c) R_(1d) X 301 1H-pyrazol-1-yl OCH₃ H H N(CH₃)305 1H-pyrazol-1-yl OCH₃ H H N(CH₃) 306 1-CH₃-1H-pyrazol-4-yl OCH₃ H HN(CH₃) 307 1H-pyrazol-4-yl OCH₃ H H N(CH₃) 3084-(1-CH₃-pyridin-2(1H)-one) OCH₃ H H N(CH₃) 309 5-pyridin-2-ol OCH₃ H HN(CH₃) 310 5-(1-CH₃-pyridin-2(1H)-one) OCH₃ H H N(CH₃) 3111-CH₃-1H-pyrazol-4-yl CH₃ H H N(CH₃) 312 4-(1-CH₃-pyridin-2(1H)-one)OCH₃ H H N(CH₃) 313 3,5-(CH₃)₂-1H-pyrazol-4-yl OCH₃ H H N(CH₃) 3141-CH₃-1H-pyrazol-4-yl CF₃ H H N(CH₃) 315 1-CH₃-1H-pyrazol-4-yl OH H HN(CH₃) 316 1H-pyrazol-1-yl OH H H N(CH₃) 317 5-(1-CH₃-pyridin-2(1H)-one)OH H H N(CH₃) 318 4-(1-CH₃-pyridin-2(1H)-one) OH H H N(CH₃) 3195-pyridin-2-ol OH H H N(CH₃) 324 H OH 1H-pyrazol- H N(CH₃) 1-yl 3251-CH₃-1H-pyrazol-4-yl H H Cl N(CH₃) 326 1-CH₃-1H-pyrazol-4-yl OH H ClN(CH₃) 327 1-CH₃-1H-pyrazol-4-yl H H Cl N(CH₃) 328 5-CH₃-oxazol-2-yl OHH OCH₃ N(CH₃) 333 CN OCH₃ H H N(CH₃) 334 CN F H H N(CH₃) 335 CO₂CH₃ F HH N(CH₃) 336 3-NHCH₃-1H-pyrazol-1-yl OCH₃ H H N(CH₃) 3384-(1-CH₃-pyridin-2(1H)-one) OCH₃ H H N(CH₃) 3394-(1-CH₃-pyridin-2(1H)-one) Cl H H N(CH₃) 340 1H-pyrazol-4-yl Cl H HN(CH₃) 341 4,5,6,7- Cl H H N(CH₃) tetrahydropyrazolo[1,5-a] pyridin-3-yl343 1-CH₃-1H-pyrazol-4-yl Cl H H O 344 6-OCH₃-pyridin-3-yl Cl H H N(CH₃)345 6-NH₂-pyridin-3-yl F H H N(CH₃) 346 3-CH₃-1H-pyrazol-5-yl F H HN(CH₃) 347 1H-pyrazol-5-yl F H H N(CH₃) 348 1H-pyrazol-4-yl H F F N(CH₃)349 1H-pyrazol-5-yl H F F N(CH₃) 350 1H-pyrazol-4-yl F F H N(CH₃) 3511H-pyrazol-5-yl F F H N(CH₃) 352 1H-pyrazol-4-yl F H F N(CH₃) 3541H-pyrazol-4-yl Cl F H N(CH₃) 356 2-NH₂-pyrimidin-4-yl Cl H H N(CH₃) 357H Cl 2-NH₂- H N(CH₃) pyrimidin-4-yl 358 2,4-(CH₃)2-thiazol-5-yl F F HN(CH₃) 359 2,4-(CH₃)2-thiazol-5-yl H F F N(CH₃) 3604-(1-CH₃-pyridin-2(1H)-one) OH H OCF₃ N(CH₃) 361 1H-pyrazol-4-yl OCH₃ HF N(CH₃) 363 1H-pyrazol-4-yl OCH₃ F F N(CH₃) 365 1H-pyrazol-1-yl Cl H HN(CH₃) 366 1H-1,2,3-triazol-1-yl Cl H H N(CH₃) 367 2H-1,2,3-triazol-2-ylCl H H N(CH₃) 368 1H-1,2,4-triazol-1-yl Cl H H N(CH₃) 3693-NH₂-1H-pyrazol-1-yl Cl H H N(CH₃) 371 1H-imidazol-1-yl Cl H H N(CH₃)372 1H-imidazol-1-yl F H H N(CH₃) 373 1H-pyrazol-5-yl OCH₃ H H N(CH₃)374 2,4-(CH₃)2-thiazol-5-yl OCH₃ H H N(CH₃) 375 pyridin-3-yl OCH₃ H HN(CH₃) 376 1H-pyrazol-4-yl F H H N(CH₃) 377 2-OCH₃-pyridin-4-yl OCH₃ H HN(CH₃) 378 6-OCH₃-pyridin-3-yl OCH₃ H H N(CH₃) 387 1H-pyrazol-1-yl OH HH N(CH₃) 388 5-(pyridin-2(1H)-one) Cl H H N(CH₃) 3893-NHCH₃-1H-pyrazol-1-yl OH H H N(CH₃) 390 1H-pyrazol-4-yl OH H F N(CH₃)391 1H-pyrazol-4-yl OH F F N(CH₃) 393 1H-pyrazol-4-yl OH H H N(CH₃) 3971H-pyrazol-4-yl OH H Cl N(CH₃) 398 1H-pyrazol-1-yl OCH₃ H H CH₂ 4101H-pyrazol-4-yl OCH₃ H H N(CH₃)

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib5) or a form thereof, wherein substituentsR_(1a), R_(1b), R_(1c), R_(1d) (each representative of the scope of R₁)and R_(4a), when present, are indicated in the table below; and, “--”indicates that one or more R_(1a), R_(1b), R_(1c), R_(1d) and R_(4a)substituents are not present:

(Ib5)

Cpd R_(1a) R_(1b) R_(1c) R_(1d) R_(4a) 353 1H-pyrazol-4-yl F F H — 3621H-pyrazol-4-yl OCH₃ H F CH₃ 370 1H-imidazol-1-yl Cl H H CH₃ 3791-CH₃-1H-pyrazol-4-yl Cl H H CH₃ 380 1H-pyrazol-4-yl Cl H H CH₃ 3841H-pyrazol-4-yl F H H CH₃ 396 1H-pyrazol-4-yl F H OH — 4051H-pyrazol-4-yl Cl H H —

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib6) or a form thereof, wherein substituentsR_(1a), R_(1b), R_(1c) and R_(1d) (each representative of the scope ofR₁), when present, are indicated in the table below; and, “--” indicatesthat one or more R_(1a), R_(1b), R_(1c) and Rid substituents are notpresent:

(1b6)

Cpd R_(1a) R_(1b) R_(1c) R_(1d) 386 1-CH₃-1H-pyrazol-4-yl OCH₃ H H 3951-CH₃-1H-pyrazol-4-yl OH H H 399 1H-pyrazol-4-yl H F F 4001H-pyrazol-4-yl OH H F

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib7) or a form thereof, wherein substituent Rib,when present, is indicated in the table below:

(1b7)

Cpd R_(1b) 304 OCH₃ 322 OH

Another embodiment of the method of the present description includes theuse of a compound of Formula (Ib) or a form thereof selected from acompound of Formula (Ib8) or a form thereof, wherein substituent R_(1b),when present, is indicated in the table below:

(Ib8)

Cpd R_(1b) 303 OCH₃ 323 OH

An embodiment of the use of a compound of Formula (I) or a form thereofincludes a method of use of a compound of Formula (I) or a form thereoffor treating or ameliorating HD in a subject in need thereof, comprisingadministering an effective amount of the compound of Formula (I) or aform thereof to the subject, selected from the group consisting of:

wherein a form of the compound is selected from the group consisting ofa prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph and tautomer formthereof.

In another aspect, the compound of Formula (I) or a form thereofincludes a compound selected from the group consisting of:

wherein a form of the compound is selected from the group consisting ofa prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph and tautomer formthereof.

Another embodiment of the use of a compound of Formula (I) or a formthereof includes a method of use of a compound of Formula (I) or a formthereof for treating or ameliorating HD in a subject in need thereof,comprising administering an effective amount of the compound of Formula(I) or a form thereof (wherein compound number (#¹) indicates that thesalt form was isolated) to the subject, selected from the groupconsisting of:

Cpd Name  16-(naphthalen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 26-(benzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  32-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)-pyridazin-3-yl)phenol  42-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzo[b]-thiophene-5-carbonitrile  56-(quinolin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 63-(benzo[b]-thiophen-2-yl)-6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)pyridazine 72-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)phenol 86-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)naphthalen-2-ol 96-(benzo[b]-thiophen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 107-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline 116-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline 12N-methyl-6-(quinolin-7-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 13N-methyl-6-(quinolin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 146-(isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 156-(isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 166-(imidazo[1,2-a]pyridin-6-yl-pyridazin-3-yl)-methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amine  17N-methyl-6-(6-phenylpyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  186-(6-(1H-pyrrol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  196-(6-(1H-pyrazol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  20methyl-(6-quinoxalin-2-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amine 21methyl-(6-quinolin-3-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amine 22N-methyl-6-(phthalazin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 236-(benzo[c][1,2,5]oxa-diazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  246-(benzo[d]thiazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 256-(2-methylbenzo-[d]oxazol-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  263-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 275-chloro-2-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 283-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)pyridazin-3-yl)naphthalen-2-ol 295-chloro-2-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)pyridazin-3-yl)phenol 304-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile  313-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalen-2-ol  32¹2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(trifluoromethyl)phenol  332-fluoro-6-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol 343,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  354,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  365-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 374,5-difluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  385-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 393-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile  401-allyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol  416-(benzo[b]thiophen-2-yl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyridazin-3-amine 42N-allyl-3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzamide  432-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  445-(5-methyl-oxazol-2-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol  455-(4-hydroxymethyl)-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  465-(1H-imidazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  475-(4-amino-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  482-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol  495-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  502-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-(2-morpholino-ethyl)-1H-pyrazol-4-yl)phenol  512-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol  525-(5-amino-1H-pyrazol-1-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol   53¹2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-yl)phenol  542-((6-((2-hydroxy-ethyl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)-5-pyrazol-1-yl)phenol  552-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  562-(6-(((2S,4R,6R)-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  572-(6-((-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 58 5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-yl-oxy)pyridazin-3-yl)phenol 592-(6-(((2S,4S)-2-methylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 60(5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-ylmethoxy)pyridazin-3-yl)phenol 612-(6-((3-fluoropiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 622-(6-(1,2,2,6,6-pentamethyl-piperidin-4-yl-oxy)-pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  635-1H-pyrazol-1-yl-2-(6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)-pyridazin-3-yl)phenol 645-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol  65¹ 2-(6-piperazin-1-yl-pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  663-(6-(azetidin-3-ylamino)-pyridazin-3-yl)naphthalen-2-ol  672-(6-(azetidin-3-ylamino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  682-(6-(3,5-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 692-(6-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  702-(6-(1,4-diazepan-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  712-(6-(4-(2-hydroxyethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 722-[6-(3,6-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 732-[6-(2,7-diazaspiro[3.5]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 742-(6-(3-(hydroxymethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 752-(6-(1,7-diazaspiro[4.4]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 762-(6-(4-amino-4-methylpiperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 772-(6-(3-(dimethylamino)piperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 782-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol  792-(6-(3,3-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 802-(6-(7-(2-hydroxyethyl)-2,7-diazaspiro[4.4]-nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol  812-[6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol   82¹3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol  835-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol 84 2-(6-piperidin-4-yl-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol  853-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalen-2-ol  86¹3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol 873-(6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol   88¹3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol  89¹ 3-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol  903-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalene-2,7-diol 913-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol  923-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol 93 tert-butyl(3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate  947-(3-amino-propoxy)-3-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)naphthalen-2-ol  95N-(3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)acetamide  967-(3-hydroxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol  977-(3-methoxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol  987-(2-morpholinoethoxy)-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalen-2-ol  993-(6-(piperidin-4-ylmethyl)pyridazin-3-yl)naphthalen-2-ol 1005-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol 1013-methoxy-2-(6-(methyl(2,2,6-trimethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol 1022-(6-((6S)-6-((S)-1-hydroxyethyl)-2,2-dimethylpiperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol 1037-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2-naphthonitrile 1043-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(piperidinylmethyl)naphthalen-2-ol 1053-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(pyrrolidinylmethyl)naphthalen-2-ol 1061-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol 1071-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol 1087-methoxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2-ol 1097-methoxy-3-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 1107-(3,6-dihydro-2H-pyran-4-yl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 1113-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)naphthalene-2-ol 1127-(difluoromethyl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 1137-((4-hydroxy-2-methylbutan-2-yl)oxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 1147-(3-hydroxy-3-methylbutoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol 1152-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)benzene-1,3-diol 1163-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 1175-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(trifluoromethoxy)phenol 1182-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethoxy)phenol 1192-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)-3-(trifluoromethoxy)phenol 1204-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one 1213-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol 1223-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)phenol 1233-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(pyridine-3-yl)phenol 1245-(1-cyclopentyl-1H-pyrazol-4-yl)-3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1253',5-dimethoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-(1,1′-biphenyl)-3-ol 1263-(benzyloxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol 1273-ethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol 1283-(cyclopropylmethoxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol 1292-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-benzo[d]imidazol-6-ol 1305-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol1315-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1323-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile1332-(6-((2,2-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol1342-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-4-yl)phenol 1352-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenol 1362-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)phenol 1374-(1H-indol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1384-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1392-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-3-yl)phenol 1404-(4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol 1414-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 1424-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)pyridin-2-ol 1435-(1H-indazol-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1444-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 1454-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 1465-fluoro-4-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1475-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-4-yl)phenol 1485-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-5-yl)phenol 1496-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one 1506-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1,4-dihydroindeno[1,2-c]-1H-pyrazol-7-ol  151¹6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one oxime 1525-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-indene-1,6-diol  153¹2-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-indeno[1,2-d]thiazol-5-ol  154¹9-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-8-ol 1554-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)benzamide 1564-(4-(hydroxymethyl)-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1575-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol 1586-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 1596-(1-(benzyloxy)isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  160¹3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  161¹4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one  162¹4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one  163¹5-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one  164¹3-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol  165¹5-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol  166¹3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol  167¹3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol 1685-(5-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1695-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol 1704-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol 1715-(6-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1725-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-(trifluoromethyl)pyridin-2-ol 1735-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 1744-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 1755-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1764-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)pyridin-2-ol 1775-(6-(dimethylamino)pyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1784-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 1792-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(pyrimidin-5-yl)phenol 1805-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-3-ol 1811-cyclopropyl-4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one 1822-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)phenol 1835-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1845-(3,6-dihydro-2H-pyran-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1855-(imidazo[1,5-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1865-(imidazo[1,2-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1872-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-methylpyridin-4-yl)phenol 1885-(1H-imidazol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1895-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1905-(imidazo[1,2-a]pyrazin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1912-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)phenol 1922-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-methyl-1H-imidazol-2-yl)phenol 1932-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-imidazol-4-yl)phenol 1942-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-imidazol-5-yl)phenol 1952-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-nitro-1H-imidazol-2-yl)phenol 1962-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-methyl-1H-imidazol-4-yl)phenol 1975-(1,2-dimethyl-1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol 1981-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1H-pyrazole-4-carboxamide 1992-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 2002-[6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 2012-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol 2024-(3-hydroxy-4-(6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 2034-(3-hydroxy-4-(6-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one 2042-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol2054-(4-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-3-hydroxyphenyl)-1-methylpyridin-2(1H)-one 2062-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol2076-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2086-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2096-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)quinolin-7-ol 2102-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2117-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol2127-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol2137-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-6-ol2147-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)isoquinolin-6-ol 2151-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2167-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1,6-diol 2176-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile 2186-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-7-ol2198-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2206-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol2212-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2223-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2233-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2247-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3-carbonitrile 2256-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(1-methyl-1H-imidazol-4-yl)quinolin-7-ol  226¹3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2276-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol2283-ethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2293-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2307-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2(1H)-one  231¹7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2(1H)-one 2324-methoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2332-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(pyrrolidin-1-yl)quinolin-7-ol 2342-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-morpholinoquinolin-7-ol 2354-(dimethylamino)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2364-ethoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2372-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1-methyl-1H-pyrazol-4-yl)quinolin-7-ol  238¹4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol  239¹7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol2406-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)quinolin-7-ol 2413-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2423-bromo-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2433-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2445-bromo-3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2456-hydroxy-1-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-4(1H)-one 2462,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 2472-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol 2483-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol 2494-methoxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2504-(azetidin-1-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2517-hydroxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolone-4-carbonitrile 2524-cyclopropyl-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-quinolin-7-ol 2534-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol  254¹2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(tetrahydro-2H-pyran-4-yl)quinolin-7-ol 2552-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(oxetan-3-yl)quinolin-7-ol 256¹4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-quinolin-7-ol 2577-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-4(1H)-one 2586-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-7-ol2597-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one 2602-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-7-ol 2617-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile 2627-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carbonitrile 2636-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2-carbonitrile 2646-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carboxamide 2657-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2-carboxamide 2666-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carboxamide 267 methyl6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carboxylate 2686-hydroxy-7-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile2697-hydroxy-6-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile270 7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol 2717-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)quinolin-6-ol 2721-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-7-ol 2731-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2741,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2757-hydroxy-3-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile 2761-amino-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2777-hydroxy-1,3-dimethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazoline-2,4(1H,3H)-dione 2786-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzo[d]oxazol-2(3H)-one 2792-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2H-indazol-6-ol 2801-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-indazol-6-ol  281¹6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-1(2H)-one 2822-ethyl-6-hydroxy-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinolin-1(2H)-one 2831-ethoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2847-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-1,6-diol2857-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)-3-phenylisoquinolin-6-ol 2863-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2873-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2883-isopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol 2893-propyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-ol2903-isopropyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-ol 291 3-methyl-7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol 2926-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 2933-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2943-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2953-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol 2964-chloro-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol 2974-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol 3007-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol3015-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3026-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol 3035-(2-methoxyquinolin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3045-(3-methoxy-naphthalen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3055-(2-methoxy-4-(1H-pyrazol-1yl)phenyl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3065-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3075-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3084-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 3095-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2-ol 3105-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 311N-methyl-5-(2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3121-methyl-4-(4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-3-(trifluoromethoxy)phenyl)pyridin-2(1H)-one 3135-(4-(3,5-dimethyl-1H-pyrazol-4-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 314N-methyl-5-(4-(1-methyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3152-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1-methyl-1H-pyrazol-4-yl)phenol 3162-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1H-pyrazol-1-yl)phenol 3175-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 3184-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 3195-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2-ol 3203-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalene-2,7-diol 3213-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)naphthalene-2,7-diol  322¹3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol 3233-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2-ol 3242-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-4-(1H-pyrazol-1-yl)phenol 3255-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3263-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol 3275-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3283-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-methyloxazol-2-yl)phenol 3292-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-thiadiazole 3302-(5-(piperazin-1-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol3315-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazole-2-amine 3326-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-7-ol 3333-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzonitrile 3343-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzonitrile 335methyl-3-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzoate 3365-(2-methoxy-4-(3-(methylamino)-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3377-methoxy-6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinoline-2-carbonitrile 3384-(3-methoxy-4-(5-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 3394-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one 3405-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3415-(2-chloro-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine  342¹N-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3432-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-yl)oxy-1,3,4-thiadiazole 3445-(2-chloro-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3455-(4-(6-aminopyridin-3-yl)-2-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3465-(2-fluoro-4-(3-methyl-1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3475-(2-fluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3485-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3495-(2,3-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3505-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3515-(2,5-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3525-(2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3532-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3545-(2-chloro-5-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3555-(3-fluoro-5-(1H-pyrazol-4-yl)pyridin-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3565-(4-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3575-(5-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3585-(4-(2,4-dimethylthiazol-5-yl)-2,5-difluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3595-(4-(2,4-dimethylthiazol-5-yl)-2,3-difluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3604-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one 3615-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3622-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3635-(2,3-difluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3646-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinolin-1-(2H)-one 3655-(2-chloro-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3665-(2-chloro-4-(1H-1,2,3-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3675-(2-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3685-(2-chloro-4-(1H-1,2,4-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3695-(4-(3-amino-1H-pyrazol-1-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3702-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3715-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3725-(2-fluoro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3735-(2-methoxy-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3745-(4-(2,4-dimethylthiazol-5-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3755-(2-methoxy-4-(pyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3765-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3775-(2-methoxy-4-(2-methoxypyridin-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3785-(2-methoxy-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 3792-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3802-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3812-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-1,3,4-thiadiazole 3821-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)morpholin-2-yl)-N,N-dimethylmethanamine 3832-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2-methyl-2,7-diazaspiro[4.5]decan-7-yl)-1,3,4-thiadiazole 3842-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole 3852-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,6-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole 3862-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole 3872-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol 3885-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2(1H)-one 3892-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(3-(methylamino)-1H-pyrazol-1-yl)phenol 3903-fluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol 3913,4-difluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol 3926-hydroxy-5-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-one 3932-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol 3942-(5-(2,6-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol 3952-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol  396¹3-fluoro-2-(5-((aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol 3973-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol 3982-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)-1,3,4-thiadiazole 3992-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole 4002-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-3-fluoro-5-(1H-pyrazol-4-yl)phenol 4014-methoxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one 4024-hydroxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one 4033-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one 4041-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one  405¹2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole  406¹2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4-thiadiazole  407¹(R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2-yl)methanol 4082-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzo[b]thiophene-5-carbonitrile 4095-(3-chlorobenzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine 4105-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine  411¹2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol  412¹2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol  413¹5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol 4145-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol  415¹2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 4165-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol 4175-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 4185-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol  419¹2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol 4206-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4215-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol  422¹2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 4235-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol  424¹5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol 425¹2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 426¹2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol 427¹2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 428¹6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  429¹2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 430¹6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine  431¹3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4322-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol  433¹2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol  434¹6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4353-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 436¹2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol 437¹3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4383-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine  439¹2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol4403-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol4412-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol442N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4432-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole4443-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine445N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4466-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine4473-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine  448¹3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4493-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine  450¹3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4515-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 4526-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4533-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol4543-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4554-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol 456¹6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4572-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine  458¹3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 4592-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 460¹3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino[pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol 4616-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy[pyridazin-3-yl}pyridin-2-ol  462¹N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine  463¹N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine  464¹3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine and  465¹6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminewherein a form of the compound is selected from the group consisting ofa prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph and tautomer formthereof.

In one aspect, the compound of Formula (I) or a form thereof includes acompound selected from the group consisting of:

411¹2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol 412¹2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 413¹5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol 414 5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 415¹2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 416 5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol 417 5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 418 5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 419¹2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol 420 6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 421 5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 422¹2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 423 5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 424¹5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol425¹2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol426¹2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol427¹ 2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol428¹6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 429¹2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol430¹6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 431¹3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 432 2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol 433¹2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol 434¹6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 435 3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine436¹2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol437¹3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 438 3-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 439¹2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol440 3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol441 2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol442 N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 443 2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole444 3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine445 N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 446 6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine447 3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 448¹3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 449 3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 450¹3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 451 5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol 452 6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 453 3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol454 3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 455 4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol456¹6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 457 2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine 458¹3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine 459 2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol460¹3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol 461 6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-2-ol 462¹N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine 463¹N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine 464¹3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine and 465¹6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminewherein a form of the compound is selected from the group consisting ofa prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph and tautomer formthereof.

Another embodiment of the use of a compound salt of Formula (I) or aform thereof includes a method of use of a compound salt of Formula (I)or a form thereof for treating or ameliorating HD in a subject in needthereof, comprising administering an effective amount of the compoundsalt of Formula (I) or a form thereof to the subject, selected from thegroup consisting of:

Cpd Name  32 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-   (trifluoromethyl)phenol hydrochloride 53 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-   yl)phenol hydrochloride  652-(6-piperazin-1-yl-pyridazin-3-yl)-5-1H- pyrazol-1-yl-phenolhydrochloride  82 3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate  863-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate  883-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol   trifluoroacetate  893-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene- 2,7-dioltrifluoroacetate 151 6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one oxime hydrochloride 1532-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-indeno[1,2-d]thiazol-5-ol hydrochloride 1549-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6- dihydroimidazo[5,1-a]isoquinolin-8-olhydrochloride 160 3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol hydrochloride 1614-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3- yl)phenyl)pyridin-2(1H)-onehydrochloride 162 4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride 1635-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride 1643-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3- yl)phenol hydrochloride 1655-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3- yl)phenol hydrochloride 1663-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H- pyrazol-4-yl)phenol hydrochloride 1673-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1- methyl-1H-pyrazol-4-yl)phenolhydrochloride 226 3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3- yl)quinolin-7-olhydrochloride 227 6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol formate 2317-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3- yl)quinolin-2(1H)-onehydrochloride 238 4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin- 6-ol formate 2397-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol hydrochloride 2542-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4- (tetrahydro-2H-pyran-4-yl)quinolin-7-olformate 256 4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)- quinolin-7-ol formate281 6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3- yl)isoquinolin-1(2H)-onehydrochloride 322 3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen- 2-ol hydrobromide 342N-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine hydrochloride 3963-fluoro-2-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)- 5-(1H-pyrazol-4-yl)phenoldihydrochloride 405 2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol- 2(1H)-yl)-1,3,4-thiadiazolehydrochloride 406 2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4- thiadiazole hydrochloride 407(R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2- yl)methanol hydrochloride 4112-{6-[8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4- yl)phenol hydrochloride412 2-[6-(8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride 4135-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3- yl}phenol hydrochloride 4152-[6-(8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride 4192-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H- pyrazol-1-yl)phenoldihydrochloride 422 2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4245-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol trihydrochloride 4252-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4262-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride 4272-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5- (1H-pyrazol-4-yl)phenoltetrahydrochloride 428 6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminetetrahydrochloride 429 2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride 4306-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminehydrochloride 431 3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine trihydrochloride433 2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino[pyridazin-3-yl}-5-(1H-pyrazol-4- yl)phenol hydrochloride 4346-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin- 3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3- amine hydrochloride 4362-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4373-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride 4392-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride 4483-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride 4503-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride 4566-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminetrihydrochloride 458 3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine trihydrochloride460 3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4- yl)pyridin-2-olhydrochloride 462 N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2- yl}piperidin-4-amine hydrochloride 463N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2- yl}piperidin-4-aminehydrochloride 464 3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazinehydrochloride and 465 6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloridewherein a form of the compound salt is selected from the groupconsisting of a prodrug, hydrate, solvate, clathrate, isotopologue,racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomerform thereof.

In one aspect, the compound salt of Formula (I) or a form thereofincludes a compound salt selected from the group consisting of:

411 2-{6-[8-azabicyclo [3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride 4122-[6-(8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride 4135-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol hydrochloride 4152-[6-(8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride 4192-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H- pyrazol-1-yl)phenoldihydrochloride 422 2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4245-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol trihydrochloride 4252-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4262-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride 4272-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5- (1H-pyrazol-4-yl)phenoltetrahydrochloride 428 6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminetetrahydrochloride 429 2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride 4306-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminehydrochloride 431 3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine trihydrochloride433 2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4- yl)phenol hydrochloride 4346-[2-methoxy-6-(1H-pyrazol-4- yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride 4362-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol trihydrochloride 4373-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride 4392-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride 4483-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride450 3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine hydrochloride 4566-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4- yl)pyridazin-3-aminetrihydrochloride 458 3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazine trihydrochloride460 3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4- yl)pyridin-2-olhydrochloride 462 N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2- yl}piperidin-4-amine hydrochloride 463N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2- yl}piperidin-4-amine hydrochloride 4643-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4- yl)oxy]pyridazinehydrochloride and 465 6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloridewherein a form of the compound salt is selected from the groupconsisting of a prodrug, hydrate, solvate, clathrate, isotopologue,racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomerform thereof.

Another embodiment of the present description includes a method of useof a compound of Formula (I) or a form thereof for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound of Formula (I) or a form thereof tothe subject.

Another embodiment of the present description includes a method of useof a compound of Formula (I) or a form thereof for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound salt of Formula (I) or a formthereof to the subject.

Another embodiment of the present description includes a use of thecompound of Formula (I) or a form thereof for treating or amelioratingHD in a subject in need thereof, comprising administering an effectiveamount of the compound of Formula (I) or a form thereof to the subject.

Another embodiment of the present description includes a use of thecompound salt of Formula (I) or a form thereof for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound salt of Formula (I) or a formthereof to the subject.

Chemical Definitions

As used herein, the term “C₁₋₄alkyl” generally refers to saturatedhydrocarbon radicals having from one to four carbon atoms in a straightor branched chain configuration, including, without limitation, methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,and the like. In some embodiments, C₁₋₄alkyl includes C₁₋₃alkyl,C₁₋₂alkyl, and the like. A C₁₋₄alkyl radical may be optionallysubstituted where allowed by available valences.

As used herein, the term “C₂₋₆alkenyl” generally refers to partiallyunsaturated hydrocarbon radicals having from two to five carbon atoms ina straight or branched chain configuration and one or more carbon-carbondouble bonds therein, including, without limitation, ethenyl, allyl,propenyl and the like. In some embodiments, C₂₋₆alkenyl includesC₂₋₄alkenyl, C₂₋₃alkenyl, and the like. A C₂₋₆alkenyl radical may beoptionally substituted where allowed by available valences.

As used herein, the term “C₁₋₄alkoxy” generally refers to saturatedhydrocarbon radicals having from one to four carbon atoms in a straightor branched chain configuration of the formula: —O—C₁₋₄alkyl, including,without limitation, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec-butoxy, tert-butoxy, and the like. In some embodiments,C₁₋₄alkoxy includes C₁₋₃alkoxy, C₁₋₂alkoxy and the like. A C₁₋₄alkoxyradical may be optionally substituted where allowed by availablevalences.

As used herein, the term “C₃₋₁₄cycloalkyl” generally refers to asaturated monocyclic, bicyclic or polycyclic hydrocarbon radical,including, without limitation, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, 1H-indanyl, indenyl,tetrahydro-naphthalenyl and the like. In some embodiments,C₃₋₁₄cycloalkyl includes C₃₋₁₀cycloalkyl, C₃₋₈cycloalkyl,C₃₋₇cycloalkyl, C₅₋₈cycloalkyl, C₉₋₁₀cycloalkyl and the like. AC₃₋₁₄cycloalkyl radical may be optionally substituted where allowed byavailable valences.

As used herein, the term “C₃₋₁₄cycloalkenyl” generally refers to apartially unsaturated monocyclic, bicyclic or polycyclic hydrocarbonradical having one or more chemically stable carbon-carbon double bondstherein, including, without limitation, cyclopropenyl, cyclobutenyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl and the like.In some embodiments, C₃₋₁₄cycloalkenyl includes C₃₋₇cycloalkenyl,C₃₋₈cycloalkenyl, C₅₋₈cycloalkenyl, C₃₋₁₀cycloalkenyl and the like. AC₃₋₁₄cycloalkenyl radical may be optionally substituted where allowed byavailable valences.

As used herein, the term “aryl” generally refers to a monocyclic,bicyclic or polycyclic aromatic carbon atom ring structure radical,including, without limitation, phenyl, naphthyl, anthracenyl, fluorenyl,azulenyl, phenanthrenyl and the like. An aryl radical may be optionallysubstituted where allowed by available valences.

As used herein, the term “heteroaryl” generally refers to a monocyclic,bicyclic or polycyclic aromatic carbon atom ring structure radical inwhich one or more carbon atom ring members have been replaced, whereallowed by structural stability, with one or more heteroatoms, such asan O, S or N atom, including, without limitation, furanyl, thienyl (alsoreferred to as thiophenyl), pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl,tetrazolyl, pyranyl, thiopyranyl, pyridinyl, pyrimidinyl, pyrazinyl,pyridazinyl, triazinyl, indolyl, indazolyl, indolizinyl, benzofuranyl,benzothienyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, 9H-purinyl,quinoxalinyl, isoindolyl, quinolinyl, isoquinolinyl, quinazolinyl,acridinyl, phthalazinyl, imidazo[1,2-a]pyridinyl,imidazo[1,5-a]pyridinyl, imidazo[5,1-a]isoquinolinyl,1,4-dihydroindeno[1,2-c]-1H-pyrazolyl, 2,3-dihydro-1H-inden-1-one,2,3-dihydro-1H-indenyl, 3,4-dihydroquinolin-2(1H)-one,5,6-dihydroimidazo[5,1-a]isoquinolinyl, 8H-indeno[1,2-d]thiazolyl,benzo[c][1,2,5]oxadiazolyl, benzo[d]oxazol-2(3H)-one,quinolin-2(1H)-one, quinazolin-4(1H)-one, quinazoline-2,4(1H,3H)-dione,benzo-[d]oxazolyl, pyrazolo[1,5-a]pyridinyl, and the like. A heteroarylradical may be optionally substituted on a carbon or nitrogen atom ringmember where allowed by available valences.

As used herein, the term “heterocyclyl” generally refers to a saturatedor partially unsaturated monocyclic, bicyclic or polycyclic carbon atomring structure radical in which one or more carbon atom ring membershave been replaced, where allowed by structural stability, with aheteroatom, such as an O, S or N atom, including, without limitation,oxiranyl, oxetanyl, azetidinyl, dihydrofuranyl, tetrahydrofuranyl,dihydrothienyl, tetrahydrothienyl, pyrrolinyl, pyrrolidinyl,dihydropyrazolyl, pyrazolinyl, pyrazolidinyl, dihydroimidazolyl,imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl,isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl,thiazolidinyl, triazolinyl, triazolidinyl, oxadiazolinyl,oxadiazolidinyl, thiadiazolinyl, thiadiazolidinyl, tetrazolinyl,tetrazolidinyl, dihydro-2H-pyranyl, dihydro-pyridinyl,tetrahydro-pyridinyl, 1,2,3,6-tetrahydropyridinyl, hexahydro-pyridinyl,dihydro-pyrimidinyl, tetrahydro-pyrimidinyl,1,4,5,6-tetrahydropyrimidinyl, dihydro-pyrazinyl, tetrahydro-pyrazinyl,dihydro-pyridazinyl, tetrahydro-pyridazinyl, piperazinyl, piperidinyl,morpholinyl, thiomorpholinyl, dihydro-triazinyl, tetrahydro-triazinyl,hexahydro-triazinyl, 1,4-diazepanyl, dihydro-indolyl, indolinyl,tetrahydro-indolyl, dihydro-indazolyl, tetrahydro-indazolyl,dihydro-isoindolyl, dihydro-benzofuranyl, tetrahydro-benzofuranyl,dihydro-benzothienyl, tetrahydro-benzothienyl, dihydro-benzimidazolyl,tetrahydro-benzimidazolyl, dihydro-benzooxazolyl,2,3-dihydrobenzo[d]oxazolyl, tetrahydro-benzooxazolyl,dihydro-benzooxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl,tetrahydro-benzooxazinyl, benzo[1,3]dioxolyl, benzo[1,4]dioxanyl,dihydro-purinyl, tetrahydro-purinyl, dihydro-quinolinyl,tetrahydro-quinolinyl, 1,2,3,4-tetrahydroquinolinyl,dihydro-isoquinolinyl, 3,4-dihydroisoquinolin-(1H)-yl,tetrahydro-isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl,dihydro-quinazolinyl, tetrahydro-quinazolinyl, dihydro-quinoxalinyl,tetrahydro-quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dioxolanyl,2,5-dihydro-1H-pyrrolyl, 4,5-dihydro-1H-imidazolyl,tetrahydro-2H-pyranyl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl,(cis)-octahydrocyclopenta[c]pyrrolyl,hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,5H-pyrrolo[3,4-b]pyridin-(7H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,(4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9-tetrahydro-1H-carbazolyl,1,2,3,4-tetrahydropyrazino[1,2-a]indolyl,2,3-dihydro-1H-pyrrolo[1,2-a]indolyl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,(3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,(3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl,(3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl,2-azabicyclo[2.2.1]heptenyl, 3-azabicyclo[3.1.0]hexanyl,3,6-diazabicyclo[3.1.0]hexanyl, (1R,5S)-3-azabicyclo[3.1.0]hexanyl,(1S,5R)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl,2,8-diazaspiro[4.5]decanyl, 3,6-diazabicyclo[3.2.1]octyl,1,4-dihydroindeno[1,2-c]pyrazolyl, dihydropyranyl, dihydropyridinyl,dihydroquinolinyl, 8H-indeno[1,2-d]thiazolyl,tetrahydroimidazo[1,2-a]pyridinyl, pyridin-2(1H)-one,(1R,5S)-8-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]oct-2-enyl and thelike. A heterocyclyl radical may be optionally substituted on a carbonor nitrogen atom ring member where allowed by available valences.

As used herein, the term “C₂₋₄alkenyl-amino-carbonyl” refers to aradical of the formula: —C(═O)—NH—C₂₋₄alkenyl.

As used herein, the term “C₁₋₄alkoxy-C₁₋₄alkoxy” refers to a radical ofthe formula: —O—C₁₋₄alkyl-O—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkoxy-carbonyl” refers to a radical ofthe formula: —C(═O)—O—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkoxy-carbonyl-amino” refers to a radicalof the formula: —NH—C(═O)—O—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkoxy-carbonyl-amino-C₁₋₄alkoxy” refersto a radical of the formula: —O—C₁₋₄alkyl-NH—C(═O)—O—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkyl-C₁₋₄alkoxy” refers to a radical ofthe formula: —O—C₁₋₄alkyl-C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkyl-amino” refers to a radical of theformula: —NH—C₁₋₄alkyl.

As used herein, the term “(C₁₋₄alkyl)₂-amino” refers to a radical of theformula: —N(C₁₋₄alkyl)₂.

As used herein, the term “C₁₋₄alkyl-amino-C₁₋₄alkoxy” refers to aradical of the formula: —O—C₁₋₄alkyl-NH—C₁₋₄alkyl.

As used herein, the term “(C₁₋₄alkyl)₂-amino-C₁₋₄alkoxy” refers to aradical of the formula: —O—C₁₋₄alkyl-N(C₁₋₄alkyl)₂.

As used herein, the term “C₁₋₄alkyl-amino-C₁₋₄alkyl” refers to a radicalof the formula: —C₁₋₄alkyl-NH—C₁₋₄alkyl.

As used herein, the term “(C₁₋₄alkyl)₂-amino-C₁₋₄alkyl” refers to aradical of the formula: —C₁₋₄alkyl-N(C₁₋₄alkyl)₂.

As used herein, the term “C₁₋₄alkyl-amino-carbonyl” refers to a radicalof the formula: —C(═O)—NH—C₁₋₄alkyl.

As used herein, the term “(C₁₋₄alkyl)₂-amino-carbonyl” refers to aradical of the formula: —C(═O)—N(C₁₋₄alkyl)₂.

As used herein, the term “C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl” refers toa radical of the formula: —C₁₋₄alkyl-C(═O)—NH—C₁₋₄alkyl.

As used herein, the term “(C₁₋₄alkyl)₂-amino-carbonyl-C₁₋₄alkyl” refersto a radical of the formula: —C₁₋₄alkyl-C(═O)—N(C₁₋₄alkyl)₂.

As used herein, the term “C₁₋₄alkyl-carbonyl” refers to a radical of theformula: —C(═O)—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkyl-carbonyl-amino” refers to a radicalof the formula: —NH—C(═O)—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkoxy” refers toa radical of the formula: —O—C₁₋₄alkyl-NH—C(═O)—C₁₋₄alkyl.

As used herein, the term “C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl” refers toa radical of the formula: —C₁₋₄alkyl-NH—C(═O)—C₁₋₄alkyl.

As used herein, the term “amino” refers to a radical of the formula:—NH₂.

As used herein, the term “amino-C₁₋₄alkoxy” refers to a radical of theformula: —O—C₁₋₄alkyl-NH₂.

As used herein, the term “amino-C₁₋₄alkyl” refers to a radical of theformula: —C₁₋₄alkyl-NH₂.

As used herein, the term “amino-carbonyl” refers to a radical of theformula: —C(═O)—NH₂.

As used herein, the term “cyano” refers to a radical of the formula:—CN.

As used herein, the term “C₃₋₇cycloalkyl-C₁₋₄alkoxy” refers to a radicalof the formula: —O—C₁₋₄alkyl-C₃₋₇cycloalkyl.

As used herein, the term “halo-C₁₋₄alkoxy” refers to a radical of theformula: —O—C₁₋₄alkyl-halo, wherein C₁₋₄alkyl may be partially orcompletely substituted where allowed by available valences with one ormore halogen atoms. In some embodiments, halo-C₁₋₄alkoxy includeshalo-C₁₋₆alkoxy, halo-C₁₋₄alkoxy and the like.

As used herein, the term “halo-C₁₋₄alkyl” refers to a radical of theformula: —C₁₋₄alkyl-halo, wherein C₁₋₄alkyl may be partially orcompletely substituted where allowed by available valences with one ormore halogen atoms. In some embodiments, halo-C₁₋₄alkyl includeshalo-C₁₋₆alkyl, halo-C₁₋₄alkyl and the like.

As used herein, the term “heteroaryl-C₁₋₄alkyl” refers to a radical ofthe formula: —C₁₋₄alkyl-heteroaryl.

As used herein, the term “heteroaryl-C₁₋₄alkyl-amino” refers to aradical of the formula: —NH—C₁₋₄alkyl-heteroaryl.

As used herein, the term “heteroaryl-C₁₋₄alkyl-amino-carbonyl” refers toa radical of the formula: —C(═O)—NH—C₁₋₄alkyl-heteroaryl.

As used herein, the term “heteroaryl-C₁₋₄alkyl-amino-carbonyl-C₁₋₄alkyl”refers to a radical of the formula:—C₁₋₄alkyl-C(═O)—NH—C₁₋₄alkyl-heteroaryl.

As used herein, the term “heteroaryl-C₁₋₄alkyl-carbonyl-amino” refers toa radical of the formula: —NH—C(═O)—C₁₋₄alkyl-heteroaryl.

As used herein, the term “heteroaryl-C₁₋₄alkyl-carbonyl-amino-C₁₋₄alkyl”refers to a radical of the formula:—C₁₋₄alkyl-NH—C(═O)—C₁₋₄alkyl-heteroaryl.

As used herein, the term “heterocyclyl-C₁₋₄alkoxy” refers to a radicalof the formula: —C₁₋₄alkoxy-heterocyclyl.

As used herein, the term “heterocyclyl-C₁₋₄alkyl” refers to a radical ofthe formula: —C₁₋₄alkyl-heterocyclyl.

As used herein, the term “hydroxyl” refers to a radical of the formula:—OH.

As used herein, the term “hydroxyl-C₁₋₄alkoxy” refers to a radical ofthe formula: —O—C₁₋₄alkyl-OH, wherein C₁₋₄alkyl may be partially orcompletely substituted where allowed by available valences with one ormore hydroxy radicals.

As used herein, the term “hydroxyl-C₁₋₄alkyl” refers to a radical of theformula: —C₁₋₄alkyl-OH, wherein C₁₋₄alkyl may be partially or completelysubstituted where allowed by available valences with one or more hydroxyradicals.

As used herein, the term “hydroxyl-C₁₋₄alkyl-amino” refers to a radicalof the formula: —NH—C₁₋₄alkyl-OH, wherein C₁₋₄alkyl may be partially orcompletely substituted where allowed by available valences with one ormore hydroxyl radicals.

As used herein, the term “hydroxyl-imino” refers to the ═NOH radical ofthe formula: C(═NOH).

As used herein, the term “oxo” refers to the radical of the formula:C═O.

As used herein, the term “phenyl-C₁₋₄alkoxy” refers to a radical of theformula: —C₁₋₄alkoxy-phenyl.

As used herein, the term “substituent” means positional variables on theatoms of a core molecule that are substituted at a designated atomposition, replacing one or more hydrogens on the designated atom,provided that the designated atom's normal valency is not exceeded, andthat the substitution results in a stable compound. Combinations ofsubstituents and/or variables are permissible only if such combinationsresult in stable compounds. A person of ordinary skill in the art shouldnote that any carbon as well as heteroatom with valences that appear tobe unsatisfied as described or shown herein is assumed to have asufficient number of hydrogen atom(s) to satisfy the valences describedor shown. In certain instances one or more substituents having a doublebond (e.g., “oxo” or “═O”) as the point of attachment may be described,shown or listed herein within a substituent group, wherein the structuremay only show a single bond as the point of attachment to the corestructure of Formula (I). A person of ordinary skill in the art wouldunderstand that, while only a single bond is shown, a double bond isintended for those substituents.

As used herein, the term “and the like,” with reference to thedefinitions of chemical terms provided herein, means that variations inchemical structures that could be expected by one skilled in the artinclude, without limitation, isomers (including chain, branching orpositional structural isomers), hydration of ring systems (includingsaturation or partial unsaturation of monocyclic, bicyclic or polycyclicring structures) and all other variations where allowed by availablevalences which result in a stable compound.

For the purposes of this description, where one or more substituentvariables for a compound of Formula (I) or a form thereof encompassfunctionalities incorporated into a compound of Formula (I), eachfunctionality appearing at any location within the disclosed compoundmay be independently selected, and as appropriate, independently and/oroptionally substituted.

As used herein, the terms “independently selected,” or “each selected”refer to functional variables in a substituent list that may occur morethan once on the structure of Formula (I), the pattern of substitutionat each occurrence is independent of the pattern at any otheroccurrence.

Further, the use of a generic substituent variable on any formula orstructure for a compound described herein is understood to include thereplacement of the generic substituent with species substituents thatare included within the particular genus, e.g., aryl may be replacedwith phenyl or naphthalenyl and the like, and that the resultingcompound is to be included within the scope of the compounds describedherein.

As used herein, the terms “each instance of” or “in each instance, whenpresent,”when used preceding a phrase such as” . . . C₃₋₁₄cycloalkyl,C₃₋₁₄cycloalkyl-C₁₋₁₄alkyl, aryl, aryl-C₁₋₄alkyl, heteroaryl,heteroaryl-C₁₋₄alkyl, heterocyclyl and heterocyclyl-C₁₋₄alkyl,” areintended to refer to the C₃₋₁₄cycloalkyl, aryl, heteroaryl andheterocyclyl ring systems when each are present either alone or as asubstituent.

As used herein, the term “optionally substituted” means optionalsubstitution with the specified substituent variables, groups, radicalsor moieties.

Compound Forms

As used herein, the term “form” means a compound of Formula (I) having aform selected from the group consisting of a free acid, free base,prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph and tautomer formthereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a free acid, free base or salt thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a salt thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is an isotopologue thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a stereoisomer, racemate, enantiomer or diastereomerthereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a tautomer thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a pharmaceutically acceptable form.

In certain embodiments described herein, the compound of Formula (I) ora form thereof is isolated for use.

As used herein, the term “isolated” means the physical state of acompound of Formula (I) or a form thereof after being isolated and/orpurified from a synthetic process (e.g., from a reaction mixture) ornatural source or combination thereof according to an isolation orpurification process or processes described herein or which are wellknown to the skilled artisan (e.g., chromatography, recrystallizationand the like) in sufficient purity to be characterized by standardanalytical techniques described herein or well known to the skilledartisan.

As used herein, the term “protected” means that a functional group in acompound of Formula (I) or a form thereof is in a form modified topreclude undesired side reactions at the protected site when thecompound is subjected to a reaction. Suitable protecting groups will berecognized by those with ordinary skill in the art as well as byreference to standard textbooks such as, for example, T. W. Greene etal, Protective Groups in organic Synthesis (1991), Wiley, New York. Suchfunctional groups include hydroxy, phenol, amino and carboxylic acid.Suitable protecting groups for hydroxy or phenol include trialkylsilylor diarylalkylsilyl (e.g., t-butyldimethylsilyl, t-butyldiphenylsilyl ortrimethylsilyl), tetrahydropyranyl, benzyl, substituted benzyl, methyl,methoxymethanol, and the like. Suitable protecting groups for amino,amidino and guanidino include t-butoxycarbonyl, benzyloxycarbonyl, andthe like. Suitable protecting groups for carboxylic acid include alkyl,aryl or arylalkyl esters. In certain instances, the protecting group mayalso be a polymer resin, such as a Wang resin or a2-chlorotrityl-chloride resin. Protecting groups may be added or removedin accordance with standard techniques, which are well-known to thoseskilled in the art and as described herein. It will also be appreciatedby those skilled in the art, although such protected derivatives ofcompounds described herein may not possess pharmacological activity assuch, they may be administered to a subject and thereafter metabolizedin the body to form compounds described herein which arepharmacologically active. Such derivatives may therefore be described as“prodrugs”. All prodrugs of compounds described herein are includedwithin the scope of the use described herein.

As used herein, the term “prodrug” means a form of an instant compound(e.g., a drug precursor) that is transformed in vivo to yield an activecompound of Formula (I) or a form thereof. The transformation may occurby various mechanisms (e.g., by metabolic and/or non-metabolic chemicalprocesses), such as, for example, by hydrolysis and/or metabolism inblood, liver and/or other organs and tissues. A discussion of the use ofprodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as NovelDelivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and inBioreversible Carriers in Drug Design, ed. Edward B. Roche, AmericanPharmaceutical Association and Pergamon Press, 1987.

In one example, when a compound of Formula (I) or a form thereofcontains a carboxylic acid functional group, a prodrug can comprise anester formed by the replacement of the hydrogen atom of the acid groupwith a functional group such as alkyl and the like. In another example,when a compound of Formula (I) or a form thereof contains a hydroxylfunctional group, a prodrug form can be prepared by replacing thehydrogen atom of the hydroxyl with another functional group such asalkyl, alkylcarbonyl or a phosphonate ester and the like. In anotherexample, when a compound of Formula (I) or a form thereof contains anamine functional group, a prodrug form can be prepared by replacing oneor more amine hydrogen atoms with a functional group such as alkyl orsubstituted carbonyl. Pharmaceutically acceptable prodrugs of compoundsof Formula (I) or a form thereof include those compounds substitutedwith one or more of the following groups: carboxylic acid esters,sulfonate esters, amino acid esters, phosphonate esters and mono-, di-or triphosphate esters or alkyl substituents, where appropriate. Asdescribed herein, it is understood by a person of ordinary skill in theart that one or more of such substituents may be used to provide acompound of Formula (I) or a form thereof as a prodrug.

One or more compounds described herein may exist in unsolvated as wellas solvated forms with pharmaceutically acceptable solvents such aswater, ethanol, and the like, and the description herein is intended toembrace both solvated and unsolvated forms.

As used herein, the term “solvate” means a physical association of acompound described herein with one or more solvent molecules. Thisphysical association involves varying degrees of ionic and covalentbonding, including hydrogen bonding. In certain instances the solvatewill be capable of isolation, for example when one or more solventmolecules are incorporated in the crystal lattice of the crystallinesolid. As used herein, “solvate” encompasses both solution-phase andisolatable solvates. Non-limiting examples of suitable solvates includeethanolates, methanolates, and the like.

As used herein, the term “hydrate” means a solvate wherein the solventmolecule is water.

The compounds of Formula (I) can form salts, which are intended to beincluded within the scope of this description. Reference to a compoundof Formula (I) or a form thereof herein is understood to includereference to salt forms thereof, unless otherwise indicated. The term“salt(s)”, as employed herein, denotes acidic salts formed withinorganic and/or organic acids, as well as basic salts formed withinorganic and/or organic bases. In addition, when a compound of Formula(I) or a form thereof contains both a basic moiety, such as, withoutlimitation an amine moiety, and an acidic moiety, such as, but notlimited to a carboxylic acid, zwitterions (“inner salts”) may be formedand are included within the term “salt(s)” as used herein.

The term “pharmaceutically acceptable salt(s)”, as used herein, meansthose salts of compounds described herein that are safe and effective(i.e., non-toxic, physiologically acceptable) for use in mammals andthat possess biological activity, although other salts are also useful.Salts of the compounds of the Formula (I) may be formed, for example, byreacting a compound of Formula (I) or a form thereof with an amount ofacid or base, such as an equivalent amount, in a medium such as one inwhich the salt precipitates or in an aqueous medium followed bylyophilization.

Pharmaceutically acceptable salts include one or more salts of acidic orbasic groups present in compounds described herein. Embodiments of acidaddition salts include, and are not limited to, acetate, ascorbate,benzoate, benzenesulfonate, bisulfate, bitartrate, borate, bromide,butyrate, chloride, citrate, camphorate, camphorsulfonate,ethanesulfonate, formate, fumarate, gentisinate, gluconate, glucaronate,glutamate, iodide, isonicotinate, lactate, maleate, methanesulfonate,naphthalenesulfonate, nitrate, oxalate, pamoate, pantothenate,phosphate, propionate, saccharate, salicylate, succinate, sulfate,tartrate, thiocyanate, toluenesulfonate (also known as tosylate),trifluoroacetate salts and the like. Certain embodiments of acidaddition salts include chloride, dichloride, trichloride, bromide,acetate, formate or trifluoroacetate salts.

Additionally, acids which are generally considered suitable for theformation of pharmaceutically useful salts from basic pharmaceuticalcompounds are discussed, for example, by P. Stahl et al, Camille G.(eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use.(2002) Zurich: Wiley-VCH; S. Berge et al, Journal of PharmaceuticalSciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics(1986) 33, 201-217; Anderson et al, The Practice of Medicinal Chemistry(1996), Academic Press, New York; and in The Orange Book (Food & DrugAdministration, Washington, D.C. on their website). These disclosuresare incorporated herein by reference thereto.

Suitable basic salts include, but are not limited to, aluminum,ammonium, calcium, lithium, magnesium, potassium, sodium and zinc salts.

All such acid salts and base salts are intended to be included withinthe scope of pharmaceutically acceptable salts as described herein. Inaddition, all such acid and base salts are considered equivalent to thefree forms of the corresponding compounds for purposes of thisdescription.

Compounds of Formula (I) and forms thereof, may further exist in atautomeric form. All such tautomeric forms are contemplated and intendedto be included within the scope of the compounds of Formula (I) or aform thereof as described herein.

The compounds of Formula (I) or a form thereof may contain asymmetric orchiral centers, and, therefore, exist in different stereoisomeric forms.The present description is intended to include all stereoisomeric formsof the compounds of Formula (I) as well as mixtures thereof, includingracemic mixtures.

The compounds described herein may include one or more chiral centers,and as such may exist as racemic mixtures (R/S) or as substantially pureenantiomers and diastereomers. The compounds may also exist assubstantially pure (R) or (S) enantiomers (when one chiral center ispresent). In one embodiment, the compounds described herein are (S)isomers and may exist as enantiomerically pure compositionssubstantially comprising only the (S) isomer. In another embodiment, thecompounds described herein are (R) isomers and may exist asenantiomerically pure compositions substantially comprising only the (R)isomer. As one of skill in the art will recognize, when more than onechiral center is present, the compounds described herein may also existas a (R,R), (R,S), (S,R) or (S,S) isomer, as defined by IUPACNomenclature Recommendations.

As used herein, the term “substantially pure” refers to compoundsconsisting substantially of a single isomer in an amount greater than orequal to 90%, in an amount greater than or equal to 92%, in an amountgreater than or equal to 95%, in an amount greater than or equal to 98%,in an amount greater than or equal to 99%, or in an amount equal to 100%of the single isomer.

In one aspect of the description, a compound of Formula (I) or a formthereof is a substantially pure (S) enantiomer form present in an amountgreater than or equal to 90%, in an amount greater than or equal to 92%,in an amount greater than or equal to 95%, in an amount greater than orequal to 98%, in an amount greater than or equal to 99%, or in an amountequal to 100%.

In one aspect of the description, a compound of Formula (I) or a formthereof is a substantially pure (R) enantiomer form present in an amountgreater than or equal to 90%, in an amount greater than or equal to 92%,in an amount greater than or equal to 95%, in an amount greater than orequal to 98%, in an amount greater than or equal to 99%, or in an amountequal to 100%.

As used herein, a “racemate” is any mixture of isometric forms that arenot “enantiomerically pure”, including mixtures such as, withoutlimitation, in a ratio of about 50/50, about 60/40, about 70/30, orabout 80/20.

In addition, the present description embraces all geometric andpositional isomers. For example, if a compound of Formula (I) or a formthereof incorporates a double bond or a fused ring, both the cis- andtrans-forms, as well as mixtures, are embraced within the scope of thedescription. Diastereomeric mixtures can be separated into theirindividual diastereomers on the basis of their physical chemicaldifferences by methods well known to those skilled in the art, such as,for example, by chromatography and/or fractional crystallization.Enantiomers can be separated by use of chiral HPLC column or otherchromatographic methods known to those skilled in the art. Enantiomerscan also be separated by converting the enantiomeric mixture into adiastereomeric mixture by reaction with an appropriate optically activecompound (e.g., chiral auxiliary such as a chiral alcohol or Mosher'sacid chloride), separating the diastereomers and converting (e.g.,hydrolyzing) the individual diastereomers to the corresponding pureenantiomers. Also, some of the compounds of Formula (I) may beatropisomers (e.g., substituted biaryls) and are considered as part ofthis description.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this description, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). Individualstereoisomers of the compounds described herein may, for example, besubstantially free of other isomers, or may be present in a racemicmixture, as described supra.

The use of the terms “salt”, “solvate”, “ester”, “prodrug” and the like,is intended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates or isotopologues of the instant compounds.

The term “isotopologue” refers to isotopically-enriched compoundsdescribed herein which are identical to those recited herein, but forthe fact that one or more atoms are replaced by an atom having an atomicmass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds described herein include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ²H, ³H,¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, ³⁵Cl and ³⁶Cl,respectively, each of which are also within the scope of thisdescription.

Certain isotopically-enriched compounds described herein (e.g., thoselabeled with ³H and ¹⁴C) are useful in compound and/or substrate tissuedistribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e., ¹⁴C)isotopes are particularly preferred for their ease of preparation anddetectability. Further, substitution with heavier isotopes such asdeuterium (i.e., ²H) may afford certain therapeutic advantages resultingfrom greater metabolic stability (e.g., increased in vivo half-life orreduced dosage requirements) and hence may be preferred in somecircumstances.

Polymorphic crystalline and amorphous forms of the compounds of Formula(I) and of the salts, solvates, hydrates, esters and prodrugs of thecompounds of Formula (I) are further intended to be included in thepresent description.

Compound Uses

The present description relates to a method of use of a compound ofFormula (I) or a form thereof for treating or ameliorating HD in asubject in need thereof, comprising administering an effective amount ofthe compound or a form thereof to the subject.

The present description further relates to use of the compound ofFormula (I) or a form thereof for treating or ameliorating HD in asubject in need thereof.

The present description further relates to use of the compound ofFormula (I) or a form thereof having activity toward HD.

The present description further relates to use of the compound ofFormula (I) or a form thereof in a combination therapy to provideadditive or synergistic activity, thus enabling the development of acombination product for treating or ameliorating HD.

In addition to monotherapeutic use, the instant compounds are useful ina combination therapy with current standard of agents, having additiveor synergistic activity with one or more known agents.

A combination therapy comprising compounds described herein incombination with one or more known drugs may be used to treat HDregardless of whether HD is responsive to the known drug.

Embodiments of the present description include the use of a compound ofFormula (I) or a form thereof in a combination therapy for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound of Formula (I) or a form thereof andan effective amount of one or more agent(s).

Embodiments of the present description include the use of a compound ofFormula (I) or a form thereof in a combination therapy for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound of Formula (I) or a form thereof andan effective amount of one or more agent(s).

In an embodiment of a use or method provided herein, compounds ofFormula (I) or a form thereof used in combination with one or moreadditional agents can be administered to a subject or contacted with asubject or patient cell(s) prior to, concurrently with, or subsequent toadministering to the subject or patient or contacting the cell with anadditional agent(s). A compound(s) of Formula (I) or a form thereof andan additional agent(s) can be administered to a subject or contactedwith a cell in single composition or different compositions. In aspecific embodiments, a compound(s) of Formula (I) or a form thereof isused in combination with gene therapy to inhibit HTT expression (using,e.g., viral delivery vectors) or the administration of another smallmolecule HTT inhibitor. In another specific embodiment, a compound(s) ofFormula (I) or a form thereof are used in combination with cellreplacement using differentiated non-mutant HTT stem cells. In anotherspecific embodiment, a compound(s) of Formula (I) or a form thereof areused in combination with cell replacement using differentiated HTT stemcells.

In one embodiment, provided herein is the use of compounds of Formula(I) or a form thereof in combination with supportive standard of caretherapies, including palliative care.

An embodiment of the present description includes the use of a compoundof Formula (I) or a form thereof in the preparation of a kit comprisingthe compound of Formula (I) or a form thereof and instructions foradministering an effective amount of the compound of Formula (I) or aform thereof and an effective amount of one or more agent(s) in acombination therapy for treating or ameliorating HD in a subject in needthereof.

Accordingly, the present description relates to use of a compound ofFormula (I) or a form thereof for treating or ameliorating HD. Inaccordance with the use of the present description, compounds that areuseful in selectively treating or ameliorating HD, have been identifiedand use of these compounds for treating or ameliorating HD has beenprovided.

One embodiment of the use of the present description relates to use of acompound of Formula (I) or a form thereof for treating or amelioratingHD in a subject in need thereof, comprising administering an effectiveamount of the compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to a methodof use of a compound of Formula (I) or a form thereof for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound to the subject.

An embodiment of the use of the present description relates to a methodof use of a compound of Formula (I) or a form thereof for treating orameliorating HD in a subject in need thereof, comprising administeringan effective amount of the compound to the subject.

An embodiment of the use of the present description relates to use of acompound of Formula (I) or a form thereof in the manufacture of amedicament for treating or ameliorating HD in a subject in need thereof,comprising administering an effective amount of the medicament to thesubject.

An embodiment of the use of the present description relates to use of acompound of Formula (I) or a form thereof in the preparation of a kitcomprising the compound of Formula (I) or a form thereof andinstructions for administering the compound for treating or amelioratingHD in a subject in need thereof.

In one respect, for each of such embodiments, the subject is treatmentnaive. In another respect, for each of such embodiments, the subject isnot treatment naive.

As used herein, the term “treating” refers to: (i) preventing a disease,disorder or condition from occurring in a subject that may bepredisposed to the disease, disorder and/or condition but has not yetbeen diagnosed as having the disease, disorder and/or condition; (ii)inhibiting a disease, disorder or condition, i.e., arresting thedevelopment thereof; and/or (iii) relieving a disease, disorder orcondition, i.e., causing regression of the disease, disorder and/orcondition.

As used herein, the term “subject” refers to an animal or any livingorganism having sensation and the power of voluntary movement, and whichrequires oxygen and organic food. Nonlimiting examples include membersof the human, primate, equine, porcine, bovine, murine, rattus, canineand feline specie. In some embodiments, the subject is a mammal or awarm-blooded vertebrate animal. In other embodiments, the subject is ahuman. As used herein, the term “patient” may be used interchangeablywith “subject” and “human”.

As used herein, the terms “effective amount” or “therapeuticallyeffective amount” mean an amount of compound of Formula (I) or a form,composition or medicament thereof effective in inhibiting theabove-noted diseases and thus producing the desired therapeutic,ameliorative, inhibitory or preventative effect in a subject in needthereof.

The dose administered to achieve an effective target plasmaconcentration may also be administered based upon the weight of thesubject or patient. Doses administered on a weight basis may be in therange of about 0.001 mg/kg/day to about 3500 mg/kg/day, or about 0.001mg/kg/day to about 3000 mg/kg/day, or about 0.001 mg/kg/day to about2500 mg/kg/day, or about 0.001 mg/kg/day to about 2000 mg/kg/day, orabout 0.001 mg/kg/day to about 1500 mg/kg/day, or about 0.001 mg/kg/dayto about 1000 mg/kg/day, or about 0.001 mg/kg/day to about 500mg/kg/day, or about 0.001 mg/kg/day to about 250 mg/kg/day, or about0.001 mg/kg/day to about 100 mg/kg/day, or about 0.001 mg/kg/day toabout 75 mg/kg/day, or about 0.001 mg/kg/day to about 50 mg/kg/day, orabout 0.001 mg/kg/day to about 40 mg/kg/day, or about 0.001 mg/kg/day toabout 30 mg/kg/day, or about 0.001 mg/kg/day to about 20 mg/kg/day, orabout 0.001 mg/kg/day to about 10 mg/kg/day, or about 0.01 mg/kg/day toabout 2000 mg/kg/day, or about 0.01 mg/kg/day to about 1500 mg/kg/day,or about 0.01 mg/kg/day to about 1000 mg/kg/day, or about 0.01 mg/kg/dayto about 600 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day,or about 0.01 mg/kg/day to about 300 mg/kg/day, or about 0.015 mg/kg/dayto about 200 mg/kg/day, or about 0.02 mg/kg/day to about 100 mg/kg/day,or about 0.025 mg/kg/day to about 100 mg/kg/day, or about 0.03 mg/kg/dayto about 100 mg/kg/day, wherein said amount is orally administered once(once in approximately a 24 hour period), twice (once in approximately a12 hour period) or thrice (once in approximately an 8 hour period) dailyaccording to subject weight.

In certain embodiments, the effective amount will be in a range of fromabout 0.001 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day toabout 500 mg/kg/day, or about 0.1 mg to about 500 mg/kg/day, or about1.0 mg/day to about 500 mg/kg/day, in single, divided, or a continuousdose for a patient or subject having a weight in a range of betweenabout 40 to about 200 kg (which dose may be adjusted for patients orsubjects above or below this range, particularly children under 40 kg).The typical adult subject is expected to have a median weight in a rangeof about 70 kg.

In another embodiment, where daily doses are adjusted based upon theweight of the subject or patient, compounds described herein may beformulated for delivery at about 0.02, 0.025, 0.03, 0.05, 0.06, 0.075,0.08, 0.09, 0.10, 0.20, 0.25, 0.30, 0.50, 0.60, 0.75, 0.80, 0.90, 1.0,1.10, 1.20, 1.25, 1.50, 1.75, 2.0, 3.0, 5.0, 10, 20, 30, 40, 50, 100,150, 200, 250, 300, 400 or 500 mg/kg/day. Daily doses adjusted basedupon the weight of the subject or patient may be administered as asingle, divided, or continuous dose. In embodiments where a dose ofcompound is given more than once per day, the dose may be administeredtwice, thrice, or more times per day.

Within the scope of the present description, the “effective amount” of acompound of Formula (I) or a form thereof for use in the manufacture ofa medicament, for use in the preparation of a pharmaceutical kit or in amethod of use for treating or ameliorating HD in a subject in needthereof is intended to include an amount in a range of from about 0.001mg/kg/day to about 3500 mg/kg/day, or about 0.001 mg/kg/day to about3000 mg/kg/day, or about 0.001 mg/kg/day to about 2500 mg/kg/day, orabout 0.001 mg/kg/day to about 2000 mg/kg/day, or about 0.001 mg/kg/dayto about 1500 mg/kg/day, or about 0.001 mg/kg/day to about 1000mg/kg/day, or about 0.001 mg/kg/day to about 500 mg/kg/day, or about0.001 mg/kg/day to about 250 mg/kg/day, or about 0.001 mg/kg/day toabout 100 mg/kg/day, or about 0.001 mg/kg/day to about 75 mg/kg/day, orabout 0.001 mg/kg/day to about 50 mg/kg/day, or about 0.001 mg/kg/day toabout 40 mg/kg/day, or about 0.001 mg/kg/day to about 30 mg/kg/day, orabout 0.001 mg/kg/day to about 20 mg/kg/day, or about 0.001 mg/kg/day toabout 10 mg/kg/day, or about 0.01 mg/kg/day to about 2000 mg/kg/day, orabout 0.01 mg/kg/day to about 1500 mg/kg/day, or about 0.01 mg/kg/day toabout 1000 mg/kg/day, or about 0.01 mg/kg/day to about 600 mg/kg/day, orabout 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day toabout 300 mg/kg/day, or about 0.015 mg/kg/day to about 200 mg/kg/day, orabout 0.02 mg/kg/day to about 100 mg/kg/day, or about 0.025 mg/kg/day toabout 100 mg/kg/day, or about 0.03 mg/kg/day to about 100 mg/kg/day,wherein said amount is administered once (once in approximately a 24hour period; i.e., “q.d.”), twice (once in approximately a 12 hourperiod; i.e., “b.i.d.” or “q.12h”), thrice (once in approximately an 8hour period; i.e., “t.i.d.” or “q.8h”), or four times (once inapproximately a 6 hour period; i.e., “q.d.s.”, “q.i.d.” or “q.6h”) dailyaccording to subject weight.

Such amounts may further include an amount in a range of from about0.001 mg to about 3500 mg administered daily; 0.001 mg to about 3000 mgadministered daily; 0.001 mg to about 2500 mg administered daily; 0.001mg to about 2000 mg administered daily; 0.001 mg to about 1500 mgadministered daily; 0.001 mg to about 1000 mg administered daily; 0.001mg to about 500 mg administered daily; 0.001 mg to about 250 mgadministered daily; 1.0 mg to about 3500 mg administered daily; 1.0 mgto about 1500 mg administered daily; 1.0 mg to about 1000 mgadministered daily; 10.0 mg to about 600 mg administered daily; 0.5 mgto about 2000 mg administered daily; or, an amount in a range of fromabout 5.0 mg to about 300 mg administered daily.

For example, the effective amount may be the amount required to treat HDin a subject or, more specifically, in a human. The effective amount fora subject will depend upon various factors, including the subject's bodyweight, size and health. Effective amounts for a given patient can bedetermined by routine experimentation that is within the skill andjudgment of the clinician.

For any compound, the effective amount can be estimated initially eitherin cell culture assays or in relevant animal models, such as a mouse,chimpanzee, marmoset or tamarin animal model. Relevant animal models mayalso be used to determine the appropriate concentration range and routeof administration. Such information can then be used to determine usefuldoses and routes for administration in humans. Therapeutic efficacy andtoxicity may be determined by standard pharmaceutical procedures in cellcultures or experimental animals, e.g., ED₅₀ (the dose therapeuticallyeffective in 50% of the population) and LD₅₀ (the dose lethal to 50% ofthe population). The dose ratio between therapeutic and toxic effects istherapeutic index, and can be expressed as the ratio, LD₅₀/ED₅₀. In someembodiments, the effective amount is such that a large therapeutic indexis achieved. In further embodiments, the dosage is within a range ofcirculating concentrations that include an ED₅₀ with little or notoxicity. The dosage may vary within this range depending upon thedosage form employed, sensitivity of the patient, and the route ofadministration.

More specifically, the concentration-biological effect relationshipsobserved with regard to a compound of Formula (I) or a form thereofindicate a target plasma concentration ranging from approximately 0.001μg/mL to approximately 50 μg/mL, from approximately 0.01 μg/mL toapproximately 20 μg/mL, from approximately 0.05 μg/mL to approximately10 μg/mL, or from approximately 0.1 μg/mL to approximately 5 μg/mL. Toachieve such plasma concentrations, the compounds described herein maybe administered at doses that vary, such as, for example, withoutlimitation, from 0.1 ng to 10,000 mg, depending upon the route ofadministration in single, divided, or continuous doses for a patientweighing between about 10 to about 100 kg (which dose may be adjustedfor patients within this weight range, particularly for children under40 kg).

The exact dosage will be determined by the practitioner, in light offactors related to the subject. Dosage and administration may beadjusted to provide sufficient levels of the active agent(s) or tomaintain the desired effect. Factors which may be taken into accountinclude the severity of the disease state, general health of thesubject, ethnicity, age, weight, gender, diet, time of day and frequencyof administration, drug combination(s), reaction sensitivities,experience with other therapies, and tolerance/response to therapy.Long-acting pharmaceutical compositions may be administered every 2, 3or 4 days, once every week, or once every two weeks depending onhalf-life and clearance rate of the particular formulation.

The compounds and compositions described herein may be administered tothe subject via any drug delivery route known in the art. Nonlimitingexamples include oral, ocular, rectal, buccal, topical, nasal,sublingual, transdermal, subcutaneous, intramuscular, intraveneous(bolus and infusion), intracerebral, and pulmonary routes ofadministration.

In one aspect, provided herein are methods for modulating the amount ofHTT (huntingtin protein), comprising contacting a human cell with acompound of Formula (I) or a form thereof. In a specific embodiment,provided herein are methods for modulating the amount of HTT, comprisingcontacting a human cell with a compound of Formula (I) or a form thereofthat modulates the expression of HTT. The human cell can be contactedwith a compound of Formula (I) or a form thereof in vitro, or in vivo,e.g., in a non-human animal or in a human. In a specific embodiment, thehuman cell is from or in a human. In another specific embodiment, thehuman cell is from or in a human with HD. In another specificembodiment, the human cell is from or in a human with HD, caused by aCAG repeat in the Htt gene, resulting in a loss of HTT expression and/orfunction. In another embodiment, the human cell is from a human with HD.In another embodiment, the human cell is in a human with HD. In oneembodiment, the compound is a form of the compound of Formula (I).

In a specific embodiment, provided herein is a method for enhancing theinhibition of mutant HTT transcribed from the Htt gene, comprisingcontacting a human cell with a compound of Formula (I) or a formthereof. The human cell can be contacted with a compound of Formula (I)or a form thereof in vitro, or in vivo, e.g., in a non-human animal orin a human. In a specific embodiment, the human cell is from or in ahuman. In another specific embodiment, the human cell is from or in ahuman with HD. In another specific embodiment, the human cell is from orin a human with HD, caused by a CAG repeat in the Htt gene, resulting ina loss of wild-type “normal” HTT expression and/or function. In anotherembodiment, the human cell is from a human with HD. In anotherembodiment, the human cell is in a human with HD. In one embodiment, thecompound is a form of the compound of Formula (I).

In another aspect, provided herein is a method for modulating theinhibition of mutant HTT transcribed from the Htt gene, comprisingadministering to a non-human animal model for HD a compound of Formula(I) or a form thereof. In a specific embodiment, provided herein is amethod for modulating the inhibition of mutant HTT transcribed from theHtt gene, comprising administering to a non-human animal model for HD acompound of Formula (I) or a form thereof. In a specific embodiment, thecompound is a form of the compound of Formula (I).

In another aspect, provided herein is a method for decreasing the amountof mutant HTT, comprising contacting a human cell with a compound ofFormula (I) or a form thereof. In a specific embodiment, provided hereinis a method for decreasing the amount of mutant HTT, comprisingcontacting a human cell with a compound of Formula (I) that inhibits thetranscription of mutant HTT (huntingtin mRNA) from the Htt gene. Inanother specific embodiment, provided herein is a method for decreasingthe amount of HTT, comprising contacting a human cell with a compound ofFormula (I) that inhibits the expression of mutant HTT transcribed fromthe Htt gene. The human cell can be contacted with a compound of Formula(I) or a form thereof in vitro, or in vivo, e.g., in a non-human animalor in a human. In a specific embodiment, the human cell is from or in ahuman. In another specific embodiment, the human cell is from or in ahuman with HD. In another specific embodiment, the human cell is from orin a human with HD, caused by a CAG repeat in the Htt gene, resulting ina loss of HTT expression and/or function. In another embodiment, thehuman cell is from a human with HD. In another embodiment, the humancell is in a human with HD. In one embodiment, the compound is a form ofthe compound of Formula (I).

In certain embodiments, treating or ameliorating HD with a compound ofFormula (I) or a form thereof (alone or in combination with anadditional agent) has a therapeutic effect and/or beneficial effect. Ina specific embodiment, treating HD with a compound of Formula (I) or aform thereof (alone or in combination with an additional agent) resultsin one, two or more of the following effects: (i) reduces or amelioratesthe severity of HD; (ii) delays onset of HD; (iii) inhibits theprogression of HD; (iv) reduces hospitalization of a subject; (v)reduces hospitalization length for a subject; (vi) increases thesurvival of a subject; (vii) improves the quality of life for a subject;(viii) reduces the number of symptoms associated with HD; (ix) reducesor ameliorates the severity of a symptom(s) associated with HD; (x)reduces the duration of a symptom associated with HD; (xi) prevents therecurrence of a symptom associated with HD; (xii) inhibits thedevelopment or onset of a symptom of HD; and/or (xiii) inhibits of theprogression of a symptom associated with HD.

Metabolites of the Compounds

Also included within the scope of the present description are the use ofin vivo metabolic products of the compounds described herein. Suchproducts may result, for example, from the oxidation, reduction,hydrolysis, amidation, esterification and the like of the administeredcompound, primarily due to enzymatic processes. Accordingly, thedescription includes the use of compounds produced by a processcomprising contacting a compound described herein with a mammaliantissue or a mammal for a period of time sufficient to yield a metabolicproduct thereof.

Such products typically are identified by preparing a radio-labeledisotopologue (e.g., ¹⁴C or ³H) of a compound described herein,administering the radio-labeled compound in a detectable dose (e.g.,greater than about 0.5 mg/kg) to a mammal such as a rat, mouse, guineapig, dog, monkey or human, allowing sufficient time for metabolism tooccur (typically about 30 seconds to about 30 hours), and identifyingthe metabolic conversion products from urine, bile, blood or otherbiological samples. The conversion products are easily isolated sincethey are “radiolabeled” by virtue of being isotopically-enriched (othersare isolated by the use of antibodies capable of binding epitopessurviving in the metabolite). The metabolite structures are determinedin conventional fashion, e.g., by MS or NMR analysis. In general,analysis of metabolites may be done in the same way as conventional drugmetabolism studies well-known to those skilled in the art. Theconversion products, so long as they are not otherwise found in vivo,are useful in diagnostic assays for therapeutic dosing of the compoundsdescribed herein even if they possess no biological activity of theirown.

Pharmaceutical Compositions

Embodiments of the present description include the use of a compound ofFormula (I) or a form thereof in a pharmaceutical composition fortreating or ameliorating HD in a subject in need thereof, comprisingadministering an effective amount of the compound of Formula (I) or aform thereof in admixture with one or more pharmaceutically acceptableexcipient(s).

An embodiment of the present description includes the use of apharmaceutical composition of the compound of Formula (I) or a formthereof in the preparation of a kit comprising the pharmaceuticalcomposition of the compound of Formula (I) or a form thereof andinstructions for administering the compound for treating or amelioratingHD in a subject in need thereof.

As used herein, the term “composition” means a product comprising thespecified ingredients in the specified amounts, as well as any productwhich results, directly or indirectly, from combination of the specifiedingredients in the specified amounts.

The pharmaceutical composition may be formulated to achieve aphysiologically compatible pH, ranging from about pH 3 to about pH 11.In some embodiments, the pharmaceutical composition is formulated toachieve a pH of from about pH 3 to about pH 7. In other embodiments, thepharmaceutical composition is formulated to achieve a pH of from aboutpH 5 to about pH 8.

The term “pharmaceutically acceptable excipient” refers to an excipientfor administration of a pharmaceutical agent, such as the compoundsdescribed herein. The term refers to any pharmaceutical excipient thatmay be administered without undue toxicity. Pharmaceutically acceptableexcipients may be determined in part by the particular composition beingadministered, as well as by the particular mode of administration and/ordosage form. Nonlimiting examples of pharmaceutically acceptableexcipients include carriers, solvents, stabilizers, adjuvants, diluents,etc. Accordingly, there exists a wide variety of suitable formulationsof pharmaceutical compositions for the instant compounds describedherein (see, e.g., Remington's Pharmaceutical Sciences).

Suitable excipients may be carrier molecules that include large, slowlymetabolized macromolecules such as proteins, polysaccharides, polylacticacids, polyglycolic acids, polymeric amino acids, amino acid copolymers,and inactive antibodies. Other exemplary excipients include antioxidantssuch as ascorbic acid; chelating agents such as EDTA; carbohydrates suchas dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose (e.g.,hydroxypropylmethylcellulose, also known as HPMC), stearic acid; liquidssuch as oils, water, saline, glycerol and ethanol; wetting oremulsifying agents; pH buffering substances; and the like. Liposomes arealso included within the definition of pharmaceutically acceptableexcipients.

The pharmaceutical compositions described herein may be formulated inany form suitable for the intended use described herein. Suitableformulations for oral administration include solids, liquid solutions,emulsions and suspensions, while suitable inhalable formulations forpulmonary administration include liquids and powders. Alternativeformulations include syrups, creams, ointments, tablets, and lyophilizedsolids which can be reconstituted with a physiologically compatiblesolvent prior to administration.

When intended for oral use for example, tablets, troches, lozenges,aqueous or oil suspensions, non-aqueous solutions, dispersible powdersor granules (including micronized particles or nanoparticles),emulsions, hard or soft capsules, syrups or elixirs may be prepared.Compositions intended for oral use may be prepared according to anymethod known to the art for the manufacture of pharmaceuticalcompositions, and such compositions may contain one or more agentsincluding sweetening agents, flavoring agents, coloring agents, andpreserving agents, in order to provide a palatable preparation.

Pharmaceutically acceptable excipients suitable for use in conjunctionwith tablets include, for example, inert diluents, such as celluloses,calcium or sodium carbonate, lactose, calcium or sodium phosphate;disintegrating agents, such as croscarmellose sodium, cross-linkedpovidone, maize starch, or alginic acid; binding agents, such aspovidone, starch, gelatin or acacia; and lubricating agents, such asmagnesium stearate, stearic acid, or talc. Tablets may be uncoated ormay be coated by known techniques including microencapsulation to delaydisintegration and adsorption in the gastrointestinal tract and therebyprovide a sustained action over a longer period. For example, a timedelay material such as glyceryl monostearate or glyceryl distearatealone or with a wax may be employed.

Formulations for oral use may be also presented as hard gelatin capsuleswhere the active ingredient is mixed with an inert solid diluent, forexample celluloses, lactose, calcium phosphate, or kaolin, or as softgelatin capsules wherein the active ingredient is mixed with non-aqueousor oil medium, such as glycerin, propylene glycol, polyethylene glycol,peanut oil, liquid paraffin, or olive oil.

In other embodiments, pharmaceutical compositions described herein maybe formulated as suspensions comprising a compound of Formula (I) or aform thereof in admixture with one or more pharmaceutically acceptableexcipient(s) suitable for the manufacture of a suspension. In yet otherembodiments, pharmaceutical compositions described herein may beformulated as dispersible powders and granules suitable for preparationof a suspension by the addition of one or more excipient(s).

Excipients suitable for use in connection with suspensions includesuspending agents, such as sodium carboxymethylcellulose,methylcellulose, hydroxypropyl methylcelluose, sodium alginate,polyvinylpyrrolidone, gum tragacanth, gum acacia, dispersing or wettingagents such as a naturally occurring phosphatide (e.g., lecithin), acondensation product of an alkylene oxide with a fatty acid (e.g.,polyoxyethylene stearate), a condensation product of ethylene oxide witha long chain aliphatic alcohol (e.g., heptadecaethyleneoxycethanol), acondensation product of ethylene oxide with a partial ester derived froma fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitanmonooleate); and thickening agents, such as carbomer, beeswax, hardparaffin, or cetyl alcohol. The suspensions may also contain one or morepreservatives such as acetic acid, methyl and/or n-propylp-hydroxy-benzoate; one or more coloring agents; one or more flavoringagents; and one or more sweetening agents such as sucrose or saccharin.

The pharmaceutical compositions described herein may also be in the formof oil-in-water emulsions. The oily phase may be a vegetable oil, suchas olive oil or arachis oil, a mineral oil, such as liquid paraffin, ora mixture of these. Suitable emulsifying agents includenaturally-occurring gums, such as gum acacia and gum tragacanth;naturally occurring phosphatides, such as soybean lecithin, esters orpartial esters derived from fatty acids; hexitol anhydrides, such assorbitan monooleate; and condensation products of these partial esterswith ethylene oxide, such as polyoxyethylene sorbitan monooleate. Theemulsion may also contain sweetening and flavoring agents. Syrups andelixirs may be formulated with sweetening agents, such as glycerol,sorbitol or sucrose. Such formulations may also contain a demulcent, apreservative, a flavoring or a coloring agent.

Additionally, the pharmaceutical compositions described herein may be inthe form of a sterile injectable preparation, such as a sterileinjectable aqueous emulsion or oleaginous suspension. Such emulsion orsuspension may be formulated according to the known art using thosesuitable dispersing or wetting agents and suspending agents which havebeen mentioned above. The sterile injectable preparation may also be asterile injectable solution or suspension in a non-toxic parenterallyacceptable diluent or solvent, such as a solution in 1,2-propanediol.The sterile injectable preparation may also be prepared as a lyophilizedpowder. Among the acceptable vehicles and solvents that may be employedare water, Ringer's solution and isotonic sodium chloride solution. Inaddition, sterile fixed oils may be employed as a solvent or suspendingmedium. For this purpose any bland fixed oil may be employed includingsynthetic mono- or di-glycerides. In addition, fatty acids such as oleicacid may likewise be used in the preparation of injectables.

The compounds described herein may be substantially insoluble in waterand sparingly soluble in most pharmaceutically acceptable proticsolvents and vegetable oils, but generally soluble in medium-chain fattyacids (e.g., caprylic and capric acids) or triglycerides and inpropylene glycol esters of medium-chain fatty acids. Thus, contemplatedin the description are compounds which have been modified bysubstitutions or additions of chemical or biochemical moieties whichmake them more suitable for delivery (e.g., increase solubility,bioactivity, palatability, decrease adverse reactions, etc.), forexample by esterification, glycosylation, PEGylation, etc.

In some embodiments, the compound described herein is formulated fororal administration in a lipid-based composition suitable for lowsolubility compounds. Lipid-based formulations can generally enhance theoral bioavailability of such compounds. As such, pharmaceuticalcompositions described herein may comprise a effective amount of acompound of Formula (I) or a form thereof, together with at least onepharmaceutically acceptable excipient selected from medium chain fattyacids or propylene glycol esters thereof (e.g., propylene glycol estersof edible fatty acids such as caprylic and capric fatty acids) andpharmaceutically acceptable surfactants, such as polysorbate 20 or 80(also referred to as Tween® 20 or Tween® 80, respectively) or polyoxyl40 hydrogenated castor oil.

In other embodiments, the bioavailability of low solubility compoundsmay be enhanced using particle size optimization techniques includingthe preparation of nanoparticles or nanosuspensions using techniquesknown to those skilled in the art. The compound forms present in suchpreparations include amorphous, partially amorphous, partiallycrystalline or crystalline forms.

In alternative embodiments, the pharmaceutical composition may furthercomprise one or more aqueous solubility enhancer(s), such as acyclodextrin. Nonlimiting examples of cyclodextrin includehydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosylderivatives of α-, β-, and γ-cyclodextrin, andhydroxypropyl-β-cyclodextrin (HPBC). In some embodiments, thepharmaceutical composition further comprises HPBC in a range of fromabout 0.1% to about 20%, from about 1% to about 15%, or from about 2.5%to about 10%. The amount of solubility enhancer employed may depend onthe amount of the compound in the composition.

Preparation of Compounds

Compounds provided herein can be prepared by those skilled in the art,such as, by the synthetic methods set forth in International ApplicationPublication Number WO2014/028459 A1, published Feb. 20, 2014,International Application Publication Number WO2014/116845 A1, publishedJul. 31, 2014, and International Application Publication NumberWO2015/017589 A1, published Feb. 5, 2015, each of which are hereinincorporated by reference.

General Schemes

The following reaction schemes illustrate methods to make compoundsdescribed herein. It is understood that one skilled in the art would beable to make these compounds by similar methods or by methods known toone skilled in the art.

In general, starting components and reagents may be commerciallyobtained from various sources such as commercial vendors, synthesizedaccording to methodology known to those skilled in the art, or preparedas described herein. It is understood that in the following description,combinations of substituents and/or variables of the depicted formulaeare permissible only if such contributions result in stable compounds.

In general, compounds of Formula (I) described herein can be synthesizedfollowing the general procedure for Scheme 1.

General Procedure for Scheme 1

The starting materials for the above reaction scheme are commerciallyavailable or can be prepared according to methods known to one skilledin the art or by methods disclosed herein. In general, the compoundsdescribed herein are prepared in the above reaction Scheme 1 as follows:a halogenated Compound 1a (wherein Hal is a halogen selected frombromine or chlorine) is reacted with a Compound 1b (wherein H is areactive hydrogen atom in an amine or alcohol X functional group,wherein X and B for a compound of Formula (I) are as described herein)using a displacement or a metal-mediated cross coupling reaction, suchas a Buchwald reaction, to provide an intermediate Compound 1c. Compound1c is carried forward and reacted with a boronate acid or boronate esterCompound 1d (where B represents a boron atom, R represents a an acid orester functional group or, when taken together with boron, form a ringsystem and A for a compound of Formula (I) is as described herein) usinga transition metal-mediated cross coupling reaction, such as a Suzukireaction, to provide a Compound of Formula (I).

In a complementary manner, compounds of Formula (I) may also besynthesized in reverse order wherein the boronate Compound 1d is reactedfirst with Compound 1a followed by reaction of the intermediate withamine Compound 1b. Other variations representing different combinationsfor substituting either or both boronate Compound 1d and amine Compound1b on Compound 1a are intended to be included within the scope of thesynthetic methodologies described herein.

SPECIFIC EXAMPLES

To assist in understanding the present description, the followingspecific examples are included. The experiments relating to thisdescription should not, of course, be construed as specifically limitingthe description and such variations of the description, now known orlater developed, which would be within the purview of one skilled in theart are considered to fall within the scope of the description asdescribed herein and hereinafter claimed.

Other than in the working examples, unless indicated to the contrary,all numbers expressing quantities of materials, reagents, reactionconditions, experimental data, and so forth used in the specificationand claims are to be understood as being modified by the term “about”.Accordingly, all such numbers represent approximations that may varydepending upon the desired properties sought to be obtained by areaction or as a result of variable experimental conditions. Therefore,within an expected range of experimental reproducibility, the term“about” in the context of the resulting data, refers to a range for dataprovided that may vary according to a standard deviation from the mean.As well, for experimental results provided, the resulting data may berounded up or down to present data consistently, without loss ofsignificant figures. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should be construed in light of thenumber of significant digits and ordinary rounding techniques.

While the numerical ranges and parameters setting forth the broad scopeof the description are approximations, the numerical values set forth inthe working examples are reported as precisely as possible. Anynumerical value, however, inherently contains certain errors necessarilyresulting from the standard deviation found in their respective testingmeasurements.

The column chromatography system used for product purification was anISCO CombiFlash™ brand chromatography system (manufactured by TeledyneIsco).

SYNTHETIC EXAMPLES

Greater details of the present description are provided with referenceto the following non-limiting examples, which are offered to more fullyillustrate the description, but are not to be construed as limiting thescope thereof. The examples illustrate the preparation of certaincompounds described herein, and the testing of these compounds in vitroand/or in vivo. Those of skill in the art will understand that thetechniques described in these examples represent techniques described bythe inventors to function well in the practice of the description, andas such constitute preferred modes for the practice thereof. However,those of skill in the art should appreciate in light of the presentdisclosure that many changes can be made to the specific methods thatare disclosed and still obtain a like or similar result withoutdeparting from the spirit and scope of the description.

As used above, and throughout this description, the followingabbreviations, unless otherwise indicated, shall be understood to havethe following meanings:

Abbreviation Meaning AcOH or HOAc acetic acid ACN or MeCN acetonitrileBn benzyl BnBr benzyl bromide BnO or OBn benzyloxy Boctert-butoxycarbonyl Boc₂O or (Boc)₂O di-tert-butyldicarbonatetBuXPhos-Pd-G3 [(2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)- 2-(2′-amino-1,1′-biphenyl)] palladium(II)methanesulfonate Cbz benzyloxycarbonyl DCE dichloroethane DCMdichloromethane (CH₂Cl₂) DIBAL-H diisobutylaluminium hydride DIPEAN,N-diisopropylethylamine DMF dimethyl formamide DMA dimethylacetamideDMAP 4-dimethylaminopyridine DMB 2,4-dimethoxybenzyl DMSOdimethylsulfoxide EA or EtOAc ethyl acetate EtOH ethanol Et₂Odiethylether HCl hydrochloric acid HPLC high performance liquidchromatography h/hr/hrs/min/s hour(s)(h, hr or hrs)/minute(s)(min/mins)/second(s) K₂CO₃ potassium carbonate KOAc potassiumacetate K₃PO₄ potassium phosphate LAH lithium aluminium hydride LC/MS,LCMS or LC-MS liquid chromatographic mass spectroscopy LDA lithiumdiisopropylamide LiHMDS lithium bis(trimethylsilyl)amide Me₄tBu-XPhosdi-tert-butyl(2′,4′,6′-triisopropyl- 3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine MeI methyliodide MeOH methanol Me₂NH or NHMe₂dimethylamine MS mass spectroscopy N₂ nitrogen Na₂SO₄ sodium sulfateNaBH(OAc)₃ sodium triacetoxyborohydride NaHMDS sodiumbis(trimethylsilyl)amide NBS N-bromosuccinimide NH₄OH ammonium hydroxideNMO N-methylmorpholine-N-oxide NMP N-methyl-2-pyrrolidone n-BuLi n-butyllithium NMR nuclear magnetic resonance Pd/C palladium on carbonPd₂(dba)₃ tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl₂[1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II) Pd(PPh₃)₄tetrakis(triphenylphosphine)palladium Pin pinacol psi pounds per squareinch pressure S-Phos 2-dicyclohexylphosphino-2′,6′- dimethoxybiphenylTBDPSCl tert-butyldiphenylchlorosilane TBS tert-butyldimethylsilyl TBSCltert-butyldimethylsilyl chloride t-BuOK potassium tert-butoxide TEA orNEt₃ triethylamine TFA trifluoroacetic acid THF tetrahydrofuran THPtetrahydro-2H-pyranyl THPO or OTHP tetrahydro-2H-pyran-2-yl-oxy TIPS-Hor TIPSH triisopropylsilane TLC thin layer chromatography TMP2,2,6,6-tetramethylpiperidinyl TMPMgCl-LiCl2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride TMSItrimethylsilyl iodide TMSOK potassium trimethylsilanolate

Example 1 (Compound 411)2-{6-[8-Azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenolhydrochloride

Step 1: 3,6-Dibromopyridazine (133.7 mg, 0.56 mmol), tert-butyl(1R,5S)-3-(methylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate (85 mg,0.28 mmol) and DIPEA (0.15 mL, 0.84 mmol) were mixed in 1 mL of ACN andheated to 100° C. for 1 h until LC-MS showed complete consumption of thestarting material. The reaction mixture was concentrated and purifiedvia column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30%MeOH), column: silica 4 g to afford tert-butyl(1S,5R)-3-[(6-bromopyridazin-3-yl)-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate(55 mg, 49.25% yield).

Step 2: tert-Butyl3-[(6-bromopyridazin-3-yl)-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate(55 mg, 0.14 mmol),4-[3-(methoxymethoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-tetrahydropyran-2-yl-pyrazole(68.82 mg, 0.17 mmol), Pd(dppf)Cl₂ (10.34 mg, 0.01 mmol), K₂CO₃ (57.98mg, 0.42 mmol) were mixed in a Schlenk tube. The reaction was degassedwith N₂ for 15 min and dioxane (2 mL) and water (0.5 mL) were added andthe reaction was heated to 90° C. for 16 h. The reaction was cooled toroom temperature, partitioned between EtOAc and water. The organiclayers were dried over Na₂SO₄, concentrated under vacuum, purified viacolumn chromatography: eluting with gradient CH₂Cl₂/EtOAc (0% to 80%),column: silica 4 g, to provide tert-butyl(1S,5R)-3-[[6-[2-(methoxymethoxy)-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]pyridazin-3-yl]-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate(52 mg, 62%) as a tan solid.

Step 3: To a solution of tert-butyl(1S,5R)-3-[[6-[2-(methoxymethoxy)-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]pyridazin-3-yl]-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate(52 mg, 0.086 mmol) in a 1 mL mixture of CH₂Cl₂ and 0.5 mL of MeOH wasadded HCl (4 mol/L) in 1,4-dioxane (0.06 mL). The reaction was stirredovernight. The precipitate was filtered, then dried under vacuum toprovide2-[6-[8-azabicyclo[3.2.1]octan-3-yl(methyl)amino]pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol;hydrochloride (15 mg, 42.25% yield) as a yellow solid.

LC-MS: 377 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.37-9.51 (m, 1H),8.87-8.96 (m, 1H), 8.31 (d, J=9.8 Hz, 1H), 8.12 (s, 2H), 7.74 (d, J=8.2Hz, 2H), 7.19-7.27 (m, 2H), 4.80-4.92 (m, 1H), 4.08-4.14 (m, 3H), 3.07(s, 3H), 2.30 (td, J=12.6, 2.8 Hz, 2H), 1.99-2.15 (m, 4H), 1.74-1.87 (m,2H)

Using the procedure described for Example 1 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 412 LC-MS: 363 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:9.24-9.34 (m, 1H), 9.09- 9.21 (m, 1H), 8.30 (d, J = 9.8 Hz, 1H), 8.09(s, 2H), 7.64-7.67 (m, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.25-7.27 (m, 1H),7.24 (s, 1H), 5.42 (br s, 2H), 4.23-4.31 (m, 1H), 4.00- 4.13 (m, 2H),2.17 (s, 4H), 1.97-2.02 (m, 2H), 1.94 (td, J = 12.6, 2.5 Hz, 2H) 413LC-MS: 393 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 9.34-9.49 (m, 1H),8.43- 8.56 (m, 1H), 8.30 (d, J = 9.8 Hz, 1H), 8.10 (s, 2H), 7.63 (s,2H), 7.19-7.30 (m, 2H), 5.77 (br s, 2H), 4.41-4.62 (m, 1H), 2.08 (dd, J= 11.7, 2.8 Hz, 2H), 1.72 (td, J = 12.1, 2.8 Hz, 2H), 1.53 (s, 6H), 1.49(s, 6H) 415 LC-MS: 364 [M + H]⁺. ¹H NMR (500 M Hz, methanol-d₄) δ: 8.61(d, J = 9.5 Hz, 1H), 8.24 (s, 2H), 7.85 (d, J = 8.2 Hz, 1H), 7.72 (d, J= 9.5 Hz, 1H), 7.38 (dd, J = 8.2, 1.6 Hz, 1H), 7.32 (d, J = 1.6 Hz, 1H),5.65 (spt, J = 5.7 Hz, 1H), 4.25 (dd, J = 3.6, 2.8 Hz, 2H), 4.17-4.32(m, 2H), 2.24 (s, 4H), 2.11 (tt, J = 11.2, 2.8 Hz, 2H) (3 hydrogenscorresponding to OH and NH unobserved) 433 LC-MS: 363 [M + H]⁺. ¹H NMR(500 M Hz, methanol-d₄) δ: 8.42 (d, J = 9.5 Hz, 1H), 8.34 (s, 2H), 7.80(d, J = 9.8 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.40 (dd, J = 8.2, 2.5Hz, 1H), 7.32 (d, J = 1.6 Hz, 1H), 4.18 (td, J = 6.9, 0.9 Hz, 1H),4.11-4.16 (m, 2H), 2.42-2.52 (m, 4H), 2.32-2.35 (m, 1H), 2.28-2.32 (m,1H), 2.15-2.25 (m, 2H), (4 hydrogens corresponding to OH and NHunobserved)

Example 2 (Compound 416)5-(5-Methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol

Step 1:3-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyltrifluoromethanesulfonate (80 mg, 0.16 mmol), (tert-butyl3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate(59 mg, 0.19 mmol), Pd(dppf)Cl₂ (7 mg, 0.01 mmol), K₂CO₃ (66 mg, 0.48mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (2 mL) and water (0.5 mL) were added and thereaction was heated to 90° C. for 16 h. The reaction was cooled to roomtemperature, partitioned between EtOAc and water. The organic layerswere dried over Na₂SO₄, concentrated under vacuum, then purified viacolumn chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30%MeOH), column: silica 4 g to provide tert-butyl4-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-methyl-1H-pyrazole-1-carboxylate(46 mg, 54%) as light brown solid.

Step 2: A solution of tert-butyl4-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-methyl-1H-pyrazole-1-carboxylate(46 mg, 0.09 mmol) in 2 mL of dry CH₂Cl₂ was cooled in ice-water bath.Boron tribromide 1.0 M in CH₂Cl₂ (0.45 mL, 0.45 mmol) was added and thereaction mixture was stirred at room temperature for 16 hours. Thereaction was quenched with 2 mL of MeOH, stirred for 30 min, thenconcentrated and purified via column chromatography: eluting withgradient CH₂Cl₂/MeOH (2.5% NH₄OH) (0% to 30% MeOH/NH₄OH), column: silica4 g, to provide tert-butyl2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(3-methyl-1H-pyrazol-4-yl)phenol(20 mg, 55%) as a yellow solid.

LC-MS: 421 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 13.74 (s, 1H),12.63-12.71 (m, 1H), 8.20 (d, J=9.5 Hz, 1H), 8.03-8.04 (m, 1H), 7.86 (d,J=8.0 Hz, 1H), 7.73-7.75 (m, 1H), 7.36 (d, J=9.5 Hz, 1H), 7.03-7.06 (m,2H), 4.90-5.05 (m, 1H), 2.92 (s, 3H), 2.43 (s, 3H), 1.43-1.54 (m, 2H),1.15-1.43 (m, 2H), 1.14 (s, 6H), 1.09 (s, 6H)

Using the procedure described for Example 2 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 414 LC-MS: 408 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 13.84(s, 1H), 8.10-8.29 (m, 2H), 7.92 (s, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.36(d, J = 9.8 Hz, 1H), 7.08-7.19 (m, 2H), 4.87-5.03 (m, 1H), 3.87 (s, 3H),2.96 (s, 3H), 1.48-1.59 (m, 2H), 1.38-1.48 (m, 2H), 1.26 (s, 6H), 1.09(s, 6H) 418 LC-MS: 422 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 12.89 (s,1H), 12.29-12.48 (m, 1H), 8.41 (dd, J = 8.8, 0.9 Hz, 1H), 7.95 (dd, J =7.9, 0.9 Hz, 1H), 7.37 (dd, J = 9.1, 1.3 Hz, 1H), 6.85-6.94 (m, 2H),5.61-5.70 (m, 1H), 2.25 (br s., 6H), 2.09 (dd, J = 11.8, 3.9 Hz, 2H),1.25-1.33 (m, 2H), 1.24 (s, 6H), 1.11 (s, 6H), (1 hydrogen correspondingto OH or NH unobserved) 451 LC-MS: 408 [M + H]⁺. ¹H NMR (500 M Hz,DMSO-d₆) δ: 13.00 (s, 1H), 12.59-12.80 (m, 1H), 8.42 (d, J = 9.5 Hz,1H), 7.94 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 9.5 Hz, 1H), 7.03-7.18 (m,2H), 5.55-5.78 (m, 1H), 2.39 (br s., 3H), 2.03-2.13 (m, 2H), 1.26-1.41(m, 2H), 1.24 (s, 6H), 1.11 (s, 6H), (1 hydrogen corresponding to OH orNH unobserved)

Example 3 (Compound 419)2-{6-[Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenoldihydrochloride

Step 1:3-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyltrifluoromethanesulfonate (335 mg, 0.67 mmol), 4-nitro-1H-pyrazole (340mg, 4.5 mmol), Pd₂(dba)₃ (67 mg, 0.07 mmol), Me₄tBu-XPhos (35 mg, 0.07mmol), K₃PO₄ (368 mg, 1.73 mmol) were mixed in a Schlenk tube. Thereaction was degassed with N₂ for 15 min and dioxane (8 mL) was addedand the reaction was heated to 90° C. for 16 h. The reaction was cooledto room temperature, filtered through celite, concentrated, purified viacolumn chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30%MeOH), column: silica 12 g, to provide6-(2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(202 mg, 65%).

LC-MS: 466 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.81-9.85 (m, 1H), 8.61(d, J=0.6 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.81 (d, J=9.8 Hz, 1H), 7.73(d, J=1.9 Hz, 1H), 7.68 (dd, J=8.2, 2.2 Hz, 1H), 7.10-7.21 (m, 1H),5.08-5.26 (m, 1H), 3.96 (s, 3H), 2.95 (s, 3H), 1.59-1.75 (m, 4H), 1.40(s, 6H), 1.33, (s, 6H), (1 hydrogen corresponding to OH or NHunobserved)

Step 2:6-(2-Methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(150 mg, 0.32 mmol), benzenethiol (33 μL, 0.32 mmol) and K₂CO₃ (44 mg,0.32 mmol) were mixed in a microwave tube. The reaction was degassedwith N₂ for 15 min and dry NMP (1.5 mL) was added. The reaction washeated in a Biotage microwave at 190° C. for 20 min, then diluted with10 mL EtOAc, and washed with water and brine. The product was dried overNa₂SO₄, concentrated under vacuum, then purified via columnchromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30% MeOH),column: silica 4 g, to provide2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-nitro-1H-pyrazol-1-yl)phenol(60 mg, 42%) as a brown solid.

LC-MS: 452 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.77 (s, 1H), 8.68 (d,J=9.8 Hz, 1H), 8.62 (s, 1H), 8.27 (d, J=8.8 Hz, 1H), 7.87-7.94 (m, 1H),7.66 (dd, J=8.5, 2.6 Hz, 1H), 7.64 (d, J=2.6 Hz, 1H), 5.03-5.22 (m, 1H),3.01 (s, 3H), 1.84-1.94 (m, 2H), 1.70-1.77 (m, 2H), 1.53 (s, 6H), 1.43(s, 6H), (2 hydrogens corresponding to OH and NH unobserved)

Using the procedure described for Example 3 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 417 LC-MS: 394 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 13.49(br s, 1H), 8.49 (d, J = 9.8 Hz, 1H), 8.39 (s, 1H), 8.10 (d, J = 8.8 Hz,1H), 7.79-7.92 (m, 1H), 7.43 (d, J = 9.5 Hz, 1H), 7.34 (d, J = 2.5 Hz,1H), 7.30 (dd, J = 8.5, 2.5 Hz, 1H), 7.12 (s, 1H), 5.61-5.71 (m, 1H),2.09 (dd, J = 12.0, 3.8 Hz, 2H), 1.25-1.32 (m, 2H), 1.24 (s, 6H), 1.11(s, 6H), (1 hydrogen corresponding to OH or NH unobserved) 421 LC-MS:409 [M + H]⁺. ¹H NMR (500 M Hz, methanol-d₄) δ: 8.31 (d, J = 9.5 Hz,1H), 7.92 (d, J = 9.1 Hz, 1H), 7.79 (d, J = 0.6 Hz, 1H), 7.44 (d, J =0.9 Hz, 1H), 7.24-7.33 (m, 3H), 5.77 (tt, J = 11.2, 4.1 Hz, 1H), 2.28(dd, J = 12.3, 4.2 Hz, 2H), 1.49 (t, J = 12.3 Hz, 2H), 1.42 (s, 6H),1.30 (s, 6H), (4 hydrogens corresponding to OH and NH unobserved) 423LC-MS: 439 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 9.71 (d, J = 0.6 Hz,1H), 8.58 (d, J = 0.6 Hz, 1H), 8.47 (d, J = 9.5 Hz, 1H), 8.14 (d, J =8.5 Hz, 1H), 7.59-7.64 (m, 2H), 7.44 (d, J = 9.5 Hz, 1H), 5.67-5.73 (m,1H), 2.18-2.28 (m, 2H), 1.45-1.56 (m, 2H), 1.37 (s, 6H), 1.27 (s, 6H),), (2 hydrogens corresponding to OH and NH unobserved)

Example 4 (Compound 424)5-(1H-Pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenoltrihydrochloride

Step 1:3-Bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine(100 mg, 0.24 mmol),(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid (66mg, 0.29 mmol), PddppfCl₂ (8 mg, 0.012 mmol), K₂CO₃ (99 mg, 0.72 mmol)were mixed in a Schlenk tube. The reaction was degassed with N₂ for 15min and dioxane (2 mL) and water (0.5 mL) were added and the reactionwas heated to 90° C. for 16 h. The reaction was cooled to roomtemperature, and partitioned between EtOAc and water. The organic layerswere dried over Na₂SO₄, then concentrated under vacuum, and purified viacolumn chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 20%MeOH), column: silica 4 g, to provide5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol(102 mg, 82%) as an off-white solid.

Step 2: A solution of5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol(102 mg, 0.196 mmol) in 2 mL of dry CH₂Cl₂ was cooled in ice-water bath.Boron tribromide 1.0 M in CH₂Cl₂(0.98 mL, 0.98 mmol) was added and thereaction mixture was stirred at room temperature for 16 hours. Thereaction was quenched with 2 mL of MeOH, stirred for 30 min, thenconcentrated and purified using preparative HPLC to provide5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol(41 mg, 66%) as an off-white solid.

LC-MS: 320 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.19 (br S, 2H), 8.54(d, J=9.6 Hz, 1H), 8.22, (d, J=9.6 Hz, 1H), 8.18 (s, 1H), 8.05 (d, J=8.8Hz, 1H), 7.25-7.29 (m, 2H), 6.92 (s, 1H), 3.85-3.92 (m, 2H), 3.38-3.41(m, 2H), 2.88-2.98 (m, 2H), (1 hydrogen corresponding to OH or NHunobserved)

Using the procedure described for Example 4 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 422 LC-MS: 334 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 11.06(br s, 1H), 8.56 (d, J = 9.2 Hz, 1H), 8.25 (d, J = 9.2 Hz, 1H), 8.20 (s,2H), 8.05 (d, J = 8.8 Hz, 1H), 7.22-7.31 (m, 2H), 6.92 (s, 1H),4.06-4.12 (m, 1H), 3.87-3.94 (m, 1H), 3.62-3.70 (m, 1H), 3.21-3.30 (m,1H), 3.07-3.12 (m, 2H), 3.03 (s, 3H), (1 hydrogen corresponding to OH orNH unobserved) 425 LC-MS: 348 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:10.94 (br S, 1H), 8.56 (d, J = 9.6 Hz, 1H), 8.26 (d, J = 9.6 Hz, 1H),8.19-8.23 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H), 7.26-7.31 (m, 2H), 6.93 (s,1H), 4.07-4.13 (m, 1H), 3.85-3.91 (m, 1H), 3.70-3.74 (m, 1H), 3.22-3.30(m, 3H), 3.08-3.14 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H), (1 hydrogencorresponding to OH or NH unobserved) 429 LC-MS: 346 [M + H]⁺. ¹H NMR(500 M Hz, methanol-d₄) δ: 1.79-1.89 (m, 1H) 1.98- 2.11 (m, 1H)2.11-2.33 (m, 2H) 2.65-2.80 (m, 1H) 3.09-3.21 (m, 1H) 4.02- 4.16 (m, 2H)7.02-7.14 (m, 1H) 7.24 (s, 2 H) 7.85-7.97 (m, 1H) 8.04 (d, J = 9.46 Hz,3H) 8.33 (d, J = 9.46 Hz, 1H)

Example 5 (Compound 427)2-[6-(Piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenoltetrahydrochloride

Step 1: 3,6-Dibromopyridazine (500 mg, 2.1 mmol),4-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole(970 mg, 2.52 mmol), Pd(dppf)Cl₂ (77 mg, 0.11 mmol), K₂CO₃ (870 mg, 6.3mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (8 mL) and water (1 mL) were added and thereaction was heated to 90° C. for 16 h. The reaction was cooled to roomtemperature, partitioned between EtOAc and water. The organic layerswere dried over Na₂SO₄, concentrated under vacuum, purified via columnchromatography: eluting with gradient hexanes/EtOAc (0% to 40% EtOAc),column: silica 4 g, to provide3-bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine(690 mg, 79%) as an off-white fluffy solid.

Step 2:3-Bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine(50 mg, 0.12 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (36 mg,0.18 mmol), potassium t-butoxide (41 mg, 0.36 mmol), tBuXPhos-Pd-G3 (10mg, 0.012 mmol) were mixed in a Schlenk tube. The reaction was degassedwith Ar then dry THF (2 mL) was added and the reaction was heated to 80°C. for 12 h. The reaction was cooled to room temperature, thenpartitioned between EtOAc and water. The organic layers were dried overNa₂SO₄, concentrated under vacuum, and purified via columnchromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 15% MeOH),column: silica 4 g, to provide tert-butyl4-((6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)amino)piperidine-1-carboxylate(45 mg, 70%) as a tan solid.

Step 3: A solution of4-((6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)amino)piperidine-1-carboxylate(45 mg, 0.084 mmol) in 2 mL of dry CH₂Cl₂ was cooled in an ice-waterbath. Boron tribromide 1.0 M in CH₂Cl₂ (0.42 mL, 0.42 mmol) was addedand the reaction mixture was stirred at room temperature for 16 hours.The reaction was quenched with 2 mL of MeOH, stirred for 30 min, thenconcentrated and purified using preparative HPLC to provide2-(6-(piperidin-4-ylamino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol (21mg, 73%) as a yellowish solid.

LC-MS: 377 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.95 (s, 2H), 8.25 (d,J=9.6 Hz, 1H), 8.09 (s, 2H), 7.69 (d, J=8.8 Hz, 1H), 7.49-7.41 (m, 1H),7.21-7.24 (m, 2H), 4.11-4.15 (m, 1H), 3.34-3.39 (m, 4H), 3.01-3.08 (m,2H), 2.11-2.17 (m, 2H), 1.79 (q, J=9.2 Hz, 2H)

Using the procedure described for Example 5 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 426 LC-MS: 351 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:9-22-9.28 (m, 2H), 8.34 (d, J = 9.6 Hz, 1H), 8.06-8.11 (m, 2H),78.5-7.89 (m, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.20-7.27 (m, 2H),4.67-4.75 (m, 2H), 3.35-3.39 (m, 2H), 3.07-3.09 (m, 2H), 3.05 (s, 3H),2.21 (q, J = 10.2 Hz, 2H), 1.83-1.88 (m, 2H) 432 LC-MS: 338 [M + H]⁺. ¹HNMR (500 M Hz, methanol-d₄) δ: 8.72 (d, J = 9.6 Hz, 1H), 8.41-8.54 (m,2H), 7.91-8.08 (m, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.2 Hz,1H), 7.38 (s, 1H), 5.51 (quint, J = 2.8 Hz, 1H), 3.30-3.46 (m, 2H),3.28-3.31 (m, 2H), 2.33-2.38 (m, 2H), 2.25-2.32 (m, 2H), (3 hydrogenscorresponding to OH and NH unobserved) 436 LC-MS: 366 [M + H]⁺. ¹H NMR(500 M Hz, DMSO-d₆) δ: 9.17-9.30 (m, 1H), 8.81- 8.95 (m, 1H), 8.49 (d, J= 9.8 Hz, 1H), 8.17 (s, 2H), 7.94 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 9.8Hz, 1H), 7.18-7.29 (m, 2H), 5.47 (spt, J = 5.7 Hz, 1H), 3.31-3.52 (m,2H), 2.41 (dd, J = 12.9, 5.7 Hz, 2H), 1.68 (q, J = 12.0 Hz, 2H), 1.34(d, J = 6.3 Hz, 6H), (1 hydrogen corresponding to OH or NH unobserved)439 LC-MS: 363 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 9.07 (s, 2H),8.28 (d, J = 10 Hz, 1H), 1.7 (s, 2H), 7.81 (d, J = 8.8 Hz, 1H), 7.73 (d,J = 9.6 Hz, 1H), 7.19-7.22 (m, 2H), 3.75-3.81 (m, 4H), 3.58-3.69 (m,4H), 1.85-1.89 (m, 4H), (1 hydrogen corresponding to OH or NHunobserved) 459 LC-MS: 349 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 10.53(s, 1H), 10.40 (s, 1H), 9.79 (br s, 1H), 9.67 (br s, 1H), 8.28 (d, J =9.6 Hz, 1H), 8.06 (s, 2H), 7.65 (d, J = 9.6 Hz, 1H), 7.58 (d, J = 8.4Hz, 1H), 7.21-7.25 (m, 1H), 4.53 (q, J = 14 Hz, 2H), 3.64 (d, J = 12.8Hz, 1H), 3.52 (d, J = 12.8 Hz, 1H), 3.37-3.40 (m, 2H), 3.15-3.24 (m,2H), 1.92-2.02 (m, 2H)

Example 6 (Compound 430)6-[2,3-Difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride

Step 1: To a RBF, equipped with a N₂ inlet, were added:6-bromo-N-methyl-N-(2,2,6,6-tetramethyl-4-piperidyl)pyridazin-3-amine(90 mg, 0.28mmol),4-[2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-tetrahydropyran-2-yl-pyrazole(128.8 mg, 0.33 mmol), Pd(PPh₃)₄ (31.8 mg, 0.03 mmol), Na₂CO₃ (87.43 mg,0.83 mmol). The reaction was degassed with N₂ for 15 min then dioxane (8mL) and water (2 mL) were added. The reaction was heated to 90° C. for16 h, then cooled to room temperature, and partitioned between EtOAc andwater. The organic layers were dried over Na₂SO₄, concentrated on arotavap, and purified via column chromatography: eluting with gradientCH₂Cl₂/MeOH (0% to 30%), column: silica 4 g to provide6-(2,3-Difluoro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(88 mg, 63%) as a grey solid.

Step 2:6-[2,3-Difluoro-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethyl-4-piperidyl)pyridazin-3-amine(88 mg, 0.17 mmol) was dissolved in MeOH (2 mL) and 4M HCl in dioxane(90 μL, 0.34 mmol) was added dropwise. The reaction mixture was stirredat room temperature for 30 min until LC-MS showed complete consumptionof starting material. The reaction mixture was concentrated underreduced pressure to provide6-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride salt.

LC-MS: 427 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.21-9.33 (m, 1H),8.27-8.43 (m, 1H), 8.20 (s, 2H), 8.01 (d, J=9.8 Hz, 1H), 7.60-7.79 (m,3H), 5.01-5.14 (m, 1H), 3.05 (s, 3H), 2.10 (td, J=13.2, 1.6 Hz, 2H),1.79 (dd, J=12.9, 4.1 Hz, 2H), 1.55 (s, 6H), 1.50 (s, 6H)

Using the procedure described for Example 6 above, additional compoundsdescribed herein may be prepared by substituting the appropriatestarting materials reagents, and reaction conditions, obtainingcompounds such as those selected from:

Cpd Data 426 LC-MS: 427 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:9.22-9.38 (m, 1H), 8.33- 8.45 (m, 1H), 8.21 (d, J = 1.9 Hz, 2H), 7.97(dd, J = 10.4, 2.8 Hz, 1H), 7.86 (d, J = 5.7 Hz, 1H), 7.81 (dd, J =11.7, 6.6 Hz, 1H), 7.54-7.63 (m, 1H), 5.09-5.16 (m, 1H), 3.03 (s, 3H),2.09 (t, J = 12.9 Hz, 2H), 1.78 (dd, J = 12.9, 3.8 Hz, 2H), 1.55 (s,6H), 1.51 (s, 6H) 431 LC-MS: 414 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:9.24-9.35 (m, 1H), 8.43- 8.58 (m, 1H), 8.22 (d, J = 1.6 Hz, 2H), 8.06(dd, J = 9.1, 1.9 Hz, 1H), 7.87 (dd, J = 12.1, 6.5 Hz, 1H), 7.83 (dd, J= 11.5, 6.5 Hz, 1H), 7.37 (d, J = 9.5 Hz, 1H), 5.77 (tt, J = 10.7, 4.1Hz, 1H), 2.33 (dd, J = 13.1, 3.9 Hz, 2H), 1.84 (dd, J = 12.9, 11.3 Hz,2H), 1.54 (s, 6H), 1.52 (s, 6H) 435 LC-MS: 378 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.57-8.58 (m, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.45(s, 2H), 8.05-8.10 (m, 1H), 7.95-7.99 (m, 1H), 7.86 (s, 1H), 7.82 (d, J= 9.5 Hz, 1H), 5.79 (tt, J = 10.4, 4.4 Hz, 1H), 2.53 (dd, J = 14.5, 4.5Hz, 2H), 1.86-2.01 (m, 2H), 1.66 (s, 6H), 1.60 (s, 6H), (2 hydrogenscorresponding to NH unobserved) 437 LC-MS: 396 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.28-9.44 (m, 1H), 8.47- 8.61 (m, 1H), 8.25 (s, 2H),8.01 (dd, J = 9.3, 2.0 Hz, 1H), 7.92 (t, J = 8.2 Hz, 1H), 7.69 (dd, J =12.8, 1.7 Hz, 1H), 7.65 (dd, J = 8.0, 1.7 Hz, 1H), 7.34 (d, J = 9.1 Hz,1H), 5.76 (tt, J = 10.7, 4.1 Hz, 1H), 2.33 (dd, J = 13.2, 3.9 Hz, 2H),1.85 (dd, J = 13.2, 10.1 Hz, 2H), 1.54 (s, 6H), 1.53 (s, 6H) 440 LC-MS:359 [M + H]⁺. ¹H NMR (500 M Hz, methanol-d₄) δ: .06 (d, J = 10.1 Hz,1H), 7.78 (dd, J = 9.5, 6.3 Hz, 1H), 7.32 (d, J = 9.8 Hz, 1H), 6.58-6.76(m, 2H), 5.11 (tt, J = 12.0, 4.1 Hz, 1H), 3.02 (s, 3H), 1.73 (dd, J =12.9, 3.5 Hz, 2H), 1.63 (t, J = 12.5 Hz, 2H), 1.43 (s, 6H), 1.27 (s,6H), (1 hydrogen corresponding to NH unobserved) 441 LC-MS: 364 [M +H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ: 1.33 (d, J = 6.62 Hz, 6H) 1.65 (q, J= 12.40 Hz, 2H) 2.42 (d, J = 12.61 Hz, 2H) 3.38-3.50 (m, 2H) 5.48 (s,1H) 6.51-6.63 (m, 1H) 7.42-7.57 (m, 3H) 7.80 (d, J = 1.58 Hz, 1H) 8.09(d, J = 8.83 Hz, 1H) 8.50 (d, J = 9.46 Hz, 1H) 8.61 (d, J = 2.52 Hz, 1H)8.76 (br s., 1H) 9.12 (br s., 1H) 13.18 (s, 1H) 442 LC-MS: 379 [M + H]⁺.¹H NMR (500 M Hz, DMSO-d₆) δ: 8.42 (s, 1H), 8.28 (dd, J = 1.6, 0.9 Hz,1H), 8.03 (dd, J = 9.1, 1.6 Hz, 1H), 7.95 (s, 1H), 7.67 (d, J = 9.1 Hz,1H), 7.14 (d, J = 9.1 Hz, 1H), 5.03-5.17 (m, 1H), 4.19 (s, 3H), 2.94 (s,3H), 1.49-1.58 (m, 2H), 1.37-1.48 (m, 2H), 1.27 (s, 6H), 1.10 (s, 6H),(1 hydrogen corresponding to NH unobserved) 443 LC-MS: 366 [M + H]⁺. ¹HNMR (500 M Hz, methanol-d₄) δ: 8.35 (s, 1H), 8.31 (dd, J = 1.6, 0.9 Hz,1H), 8.11 (d, J = 9.1 Hz, 1H), 7.99 (dd, J = 9.1, 1.9 Hz, 1H), 7.75 (dt,J = 9.1, 0.9 Hz, 1H), 7.21 (d, J = 9.5 Hz, 1H), 5.81 (tt, J = 11.2, 4.1Hz, 1H), 4.27 (s, 3H), 2.28 (dd, J = 12.6, 4.1 Hz, 2H), 1.48 (t, J =12.3 Hz, 2H), 1.41 (s, 6H), 1.30 (s, 6H), (1 hydrogen corresponding toNH unobserved) 445 LC-MS: 379 [M + H]⁺. ¹H NMR (500 M Hz, acetone-d₆) δ:8.52 (dt, J = 7.0, 1.1 Hz, 1H), 8.13 (dt, J = 8.8, 1.3 Hz, 1H), 7.66 (d,J = 9.8 Hz, 1H), 7.28 (ddd, J = 9.0, 6.8, 1.3 Hz, 1H), 7.13 (d, J = 9.5Hz, 1H), 6.89 (td, J = 6.9, 1.4 Hz, 1H), 5.22 (tt, J = 12.3, 3.5 Hz,1H), 3.04 (s, 3H), 2.63 (s, 3H), 1.67 (dd, J = 12.3, 3.5 Hz, 2H), 1.56(t, J = 12.3 Hz, 2H), 1.36 (s, 6H), 1.18 (s, 6H), (1 hydrogencorresponding to NH unobserved) 446 LC-MS: 352 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 9.14 (dd, J = 1.6, 0.9 Hz, 1H), 7.98 (dd, J = 9.5,1.9 Hz, 1H), 7.94 (t, J = 0.9 Hz, 1H), 7.89 (d, J = 9.5 Hz, 1H), 7.63(dt, J = 9.5, 0.8 Hz, 1H), 7.60 (d, J = 1.3 Hz, 1H), 7.14 (d, J = 9.5Hz, 1H), 5.34 (tt, J = 12.6, 3.5 Hz, 1H), 1.67 (dd, J = 12.3, 3.8 Hz,2H), 1.55 (t, J = 12.1 Hz, 2H), 1.36 (s, 6H), 1.17 (s, 6H), (1 hydrogencorresponding to NH unobserved) 447 LC-MS: 394 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 8.47 (d, J = 2.5 Hz, 1H), 8.05 (d, J = 9.1 Hz, 1H),7.98 (d, J = 8.5 Hz, 1H), 7.76 (d, J = 1.9 Hz, 1H), 7.70 (d, J = 2.2 Hz,1H), 7.59 (dd, J = 8.5, 2.2 Hz, 1H), 7.06 (d, J = 9.1 Hz, 1H), 6.57 (dd,J = 2.4, 1.7 Hz, 1H), 5.85 (tt, J = 11.3, 4.1 Hz, 1H), 2.21 (dd, J =12.1, 3.9 Hz, 2H), 2.04-2.08 (m, 2H), 1.35 (s, 6H), 1.18 (s, 6H), (2hydrogens corresponding to OH and NH unobserved) 452 LC-MS: 409 [M +H]⁺. ¹H NMR (500 M Hz, acetone-d₆) δ: 7.59 (dd, J = 8.5, 6.0 Hz, 1H),7.46 (s, 2H), 7.31 (dd, J = 10.1, 2.5 Hz, 1H), 7.15 (td, J = 8.5, 2.5Hz, 1H), 7.04 (d, J = 9.5 Hz, 1H), 6.91 (d, J = 9.5 Hz, 1H), 5.23 (tt, J= 12.3, 2.8 Hz, 1H), 3.00 (s, 3H), 1.65 (dd, J = 12.3, 3.5 Hz, 2H), 1.51(t, J = 12.1 Hz, 2H), 1.33 (s, 6H), 1.15 (s, 6H), (2 hydrogenscorresponding to NH unobserved) 455 LC-MS: 344 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.17 (d, J = 9.5 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H),7.19 (d, J = 9.5 Hz, 1H), 6.44 (dd, J = 8.7, 2.4 Hz, 1H), 6.41 (d, J =2.5 Hz, 1H), 5.71 (tt, J = 11.0, 3.8 Hz, 1H), 2.23 (dd, J = 12.6, 4.1Hz, 2H), 1.40- 1.47 (m, 2H), 1.39 (s, 6H), 1.27 (s, 6H), (3 hydrogenscorresponding to OH and NH unobserved) 456 LC-MS: 425 [M + H]⁺. ¹H NMR(500 M Hz, DMSO-d₆) δ: 9.23-9.39 (m, 1H), 8.39- 8.52 (m, 1H), 8.26 (s,2H), 8.00-8.08 (m, 1H), 7.93 (s, 1H), 7.81-7.85 (m, 1H), 7.78 (d, J =7.9 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 4.95-5.03 (m, 1H), 3.08 (s, 3H),2.13 (t, J = 12.9 Hz, 2H), 1.81 (dd, J = 12.9, 3.5 Hz, 2H), 1.56 (s,6H), 1.52 (s, 6H) 458 LC-MS: 414 [M + H]⁺. ¹H NMR (500 M Hz, DMSO-d₆) δ:8.70-9.36 (m, 1H), 8.29 (s, 2H), 7.85 (d, J = 9.1 Hz, 1H), 7.60 (d, J =9.5 Hz, 1H), 7.33-7.39 (m, 1H), 5.59-5.68 (m, 1H), 2.24-2.33 (m, 2H),1.72-1.82 (m, 2H), 1.50 (s, 6H), 1.48 (s, 6H), (2 hydrogenscorresponding to NH unobserved)

Example 7 (Compound 434)6-[2-Methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride

6-(2-Methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(6 mg) was dissolved in 1 mL of 4N HCl/dioxane and the resulting mixturewas stirred at RT for 20 minutes. The mixture was evaporated andtriturated with ether to provide6-(2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine4 mg, 75%).

LC-MS: 422 [M+H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.42-8.47 (m, 1H),8.33-8.42 (m, 2H), 8.09-8.17 (m, 1H), 7.99-8.08 (m, 1H), 7.50-7.56 (m,1H), 5.0 (m, 1H), 4.16 (s, 3H), 3.20 (s, 3H), 1.94-2.15 (m, 4H), 1.65(s, 6H), 1.57 (s, 6H)

Example 8 (Compound 460)3-{6-[Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(H-pyrazol-4-yl)pyridin-2-olhydrochloride

Step 1:6-Chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(280 mg, 1.0 mmol) was dissolved in 10 mL, a mixture of dioxane andwater (4:1). To the solution was added sodium carbonate (190 mg, 3 eq),(6-chloro-2-methoxypyridin-3-yl)boronic acid (190 mg, 1 eq) andPd(Ph₃P)₄ (70 mg, 0.1 eq). The reaction mixture was stirred at 90° C.for 16 h, then applied to a column and purified using DCM/MeOH to yield(133 mg, 55%)6-(6-chloro-2-methoxypyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine.

LC-MS: 390 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.25 (d, J=7.88 Hz, 1H),7.83 (d, J=9.77 Hz, 1H), 7.24 (d, J=7.88 Hz, 1H), 7.11 (d, J=9.77 Hz,1H), 5.00-5.24 (m, 1H), 3.93 (s, 3H), 2.87-2.96 (m, 3H), 1.40-1.57 (m,4H), 1.21-1.29 (m, 7H), 1.10 (br s, 6H

Step 2:6-(6-Chloro-2-methoxypyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(90 mg) was dissolved in a mixture of dioxane and water (4:1, 5 mL). Tothe solution was added sodium carbonate (100 mg, 3 eq),1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(70 mg, 1.1 eq) and Pd(Ph₃P)₄ (27 mg, 0.1 eq). The reaction mixture wasstirred at 90° C. for 16 h, then purified by column chromatography usingDCM/MeOH to yield 80 mg (68%) of6-(2-methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine.

Step 3:6-(2-Methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine(45 mg) was dissolved in 4 mL of 4N HCl/dioxane and the resultingmixture was heated for 2 hours at 60° C.F. The resulting mixture wasevaporated and triturated with ether to provide3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-6-(1H-pyrazol-4-yl)pyridin-2-ol(24 mg, 61%).

LC-MS: 408 [M+H]+; ¹H NMR (500 MHz, methanol-d₄) δ: 8.62-8.69 (m, 1H),8.55-8.61 (m, 1H), 8.39 (s, 2H), 7.95-8.06 (m, 1H), 7.04-7.14 (m, 1H),5.02-5.24 (m, 1H), 3.18 (s, 3H), 2.03 (s, 4H), 1.67 (s, 6H), 1.57 (s,6H)

Using the procedure described for Example 8 above, an additionalcompound described herein may be prepared by substituting theappropriate starting materials reagents, and reaction conditions,obtaining compounds such as those selected from:

Cpd Data 461 LC-MS: 395 [M + H]⁺. ¹H NMR (500 M Hz, methanol-d₄) δ: 8.46(d, J = 9.5 Hz, 1H), 8.33-8.42 (m, 1H), 8.29 (d, J = 7.6 Hz, 1H),8.10-8.23 (m, 1H), 7.20 (d, J = 9.1 Hz, 1H), 6.86 (d, J = 7.3 Hz, 1H),5.84 (tt, J = 10.4, 3.8 Hz, 1H), 2.49 (dd, J = 13.9, 4.1 Hz, 2H), 1.86(dd, J = 13.9, 10.4 Hz, 2H), 1.65 (s, 6H), 1.56 (s, 6H), (3 hydrogenscorresponding to OH and NH unobserved)

BIOLOGICAL EXAMPLES

The following in vitro biological examples demonstrate the usefulness ofthe compounds of the present description for treating Huntington'sdisease.

To describe in more detail and assist in understanding the presentdescription, the following non-limiting biological examples are offeredto more fully illustrate the scope of the description and are not to beconstrued as specifically limiting the scope thereof. Such variations ofthe present description that may be now known or later developed, whichwould be within the purview of one skilled in the art to ascertain, areconsidered to fall within the scope of the present description and ashereinafter claimed.

Example 1

Development and Validation of Meso Scale Discovery (MSD) Assay toQuantify Mutant and Total Huntingtin Protein (HTT)—Best Pair Analysisfor Endogenous HTT Detection

To identify orally bioavailable small molecules useful for HTTreduction, high throughput ELISA methods to detect and measure bothtotal HTT (wild-type and mutant)(tHTT) and mutant HTT (mHTT) in cellsand tissues from HD patients and animal models are needed. The methoddescribed herein permits relatively high throughput protein measurementof tHTT and mHTT levels in cells and tissues from HD patients and in HDanimal models. The ELISA method described herein enables screening ofmolecules for their ability to decrease the level of HTT and to identifyand optimize small molecules for use in treating HD.

To determine the combination of antibodies that detect HTT (wild typeand mutant) in a sensitive, high throughput format, multiplecommercially available antibodies (Table 1) were screened incapture/detection combinations.

Protocol for Best Pair Analysis for Antibody Comparison in DetectingTotal and Mutant HTT in Cells

-   1. Cells were cultured in a cell culture-compatible 96-well plate.-   2. The medium was removed and 50-100 μL of lysis buffer per well    (composition described below) was added to cells to provide a “cell    lysate”. The plate was placed on a shaker at 4° C. for 30 minutes,    then stored at −20° C.-   3. A Capture Antibody Diluent was prepared by diluting the capture    antibody in PBS for standard plates as described in the plate    layout, then 30 μL of the Capture Antibody Diluent was added per    well. The plate was sealed and incubated at 4° C. overnight.-   4. The plate was washed 3× with 200 μL of Wash Buffer. Blocking    Buffer (150 μL per well) was added, then the plate was sealed and    incubated on a plate shaker for 3-4 hours at room temperature (RT).-   5. The Blocking Buffer was decanted and the plate was washed 3× with    200 μL of Wash Buffer. The cell lysate (25 μL per well) was then    added. The plate was sealed and incubated at 4° C. overnight.-   6. A First Detection Antibody Diluent was prepared by diluting a    first detection antibody for pairing in an Assay Antibody Diluent.    The plate was washed 3× with 200 μL of Wash Buffer, then 25 μL of    the First Detection Antibody Diluent was added per well. The plate    was sealed and incubated on a plate shaker for 1 hour at RT.-   7. A Second Detection Antibody Diluent was prepared by diluting a    second detection antibody for pairing in an Assay Antibody Diluent.    The plate was washed 3× with 200 μL of Wash Buffer, then 25 μL of    the Second Detection Antibody Diluent was added per well. The plate    was sealed and incubated on a plate shaker for 1 hour at RT.-   8. The Read Buffer was diluted 4×. The plate was washed 3× with 200    μL of Wash Buffer, then 150 μL of the Read Buffer was added per    well. The plate were read immediately following.

The various commercially available antibodies screened in the Best PairAnalysis, providing different capture/detection combinations are shownin Table 1. The capture/detection antibody pairs evaluated are shown inTable 2. The two antibody pairs that gave the maximum spread of values(higher signal to noise ratio) were selected for polyglutamine-expanded(mHTT) and total human HTT detection.

TABLE 1 Species ID Antibody Epitope monoclonal MAB2166 Huntingtinfragment from aa mouse 181-810 as a fusion protein monoclonal MAB2174Huntingtin fusion protein 549-679, rat fused to Glutathione S-tranferasemonoclonal MAB5374 GST fusion protein from the first 256 mouse aminoacids from human huntingtin with the deletion of the polyglutamine tractgoat sc-8767 Peptide mapping near the N-terminus of polyclonalHuntingtin of human origin (N18) monoclonal P1874 GST human Huntingtin(N-terminal mouse fragment of 171 amino acids containing 65Q) monoclonalMAB1574 Homopolymeric glutamine stretch mouse monoclonal #5656SSynthetic peptide corresponding rabbit to residues surrounding Pro1220of human huntingtin protein monoclonal MW1 DRPLA-19Q mouse

TABLE 2 Signal to Pair HTT MSD ID Noise ratio Capture/Detection TotalMAB2166/MAB2174 95 Capture/Detection Total MAB2166/sc-8767 6Capture/Detection Total sc-8767/#5656 5 Capture/Detection TotalMAB2166/#5656S 483 Capture/Detection Mutant MAB5374/#5656S 8Capture/Detection Mutant MAB1574/#5656S 25 Capture/Detection MutantP1874/#5656S 20 Capture/Detection Mutant MW1/#5656S 45

Characteristics for Best Pair capture/detection antibody pairs are thosecombinations that give minimum background and maximum signal. Suchhighly sensitive ELISA assays would be useful to detect HTT in thecontext of drug discovery for screening agents (small and largemolecules and gene therapies) and for use in detecting HTT as abiomarker in clinical studies. Such capture/detection antibody pairs forquantifying total HTT are selected from MAB2166/MAB2174 andMAB2166/#5656S. Such capture/detection antibody pairs for quantifyingmutant HTT are selected from MAB1574/#5656S, P1874/#5656S andMW1/#5656S. The antibody pair for mHTT (MW1/#5656S) and the other fortotal HTT (MAB2166/#5656S) from this analysis were further optimized andvalidated to provide high-throughput assays that enabled HTT detectionin patient fibroblasts and lymphocytes.

The Endogenous Huntingtin Protein assay used in Example 2 was developedusing the Best Pair antibodies identified in Table 2, providing highlysensitive, high-throughput detection assays for polyglutamine-expanded(mHTT) and total human HTT in multiple cell systems. The platform usedfor the assay is the ELISA-based Meso Scale Discovery (MSD)electrochemiluminescence assay platform.

Example 2

Endogenous Huntingtin Protein Assay

Meso Scale Discovery (MSD) 96-well or 384-well plates were coatedovernight at 4° C. with MW1 (expanded polyglutamine) or MAB2166monoclonal antibody (for capture) at a concentration of 1 μg/mL in PBS(30 μL per well). Plates were then washed three times with 300 μL washbuffer (0.05% Tween-20 in PBS) and blocked (100 μL blocking buffer; 5%BSA in PBS) for 4-5 hours at room temperature with rotational shakingand then washed three times with wash buffer.

Samples (25 μL) were transferred to the antibody-coated MSD plate andincubated overnight at 4° C. After removal of the lysates, the plate waswashed three times with wash buffer, and 25 μL of #5656S (Cellsignaling; rabbit monoclonal) secondary antibody (diluted to 0.25 μg/mLin 0.05% Tween-20 in blocking buffer) was added to each well andincubated with shaking for 1 Hour at room temperature. Followingincubation with the secondary antibody, the wells were rinsed with washbuffer after which 25 μL of goat anti-rabbit SULFO TAG secondarydetection antibody (required aspect of the MSD system) (diluted to 0.25μg/mL in 0.05% Tween-20 in blocking buffer) was added to each well andincubated with shaking for 1 hour at room temperature. After rinsingthree times with wash buffer, 150 μL of read buffer T with surfactant(MSD) were added to each empty well, and the plate was imaged on a SI6000 imager (MSD) according to manufacturers' instructions provided for96- or 384-well plates. The resulting IC₅₀ values (μM) for compoundstested are shown in Table 3.

As shown in Table 3, test compounds described herein had the followingIC₅₀ values, an IC₅₀ value between >3 μM and <9 μM is indicated by asingle star (*), an IC₅₀ value between >1 μM and <3 μM is indicated bytwo stars (**), an IC₅₀ value between >0.5 μM and <1 μM is indicated bythree stars (***), an IC₅₀ value between >0.1 μM and <0.5 μM isindicated by four stars (****) and an IC₅₀ value of <0.1 μM is indicatedby five stars (*****).

TABLE 3 Cpd IC₅₀ Cpd IC₅₀ Cpd IC₅₀ 16 * 413 ***** 441 * 26 **** 414***** 442 * 31 *** 415 ***** 443 * 460 * 416 ***** 444 * 39 * 417 *****445 * 44 ***** 418 ***** 446 * 46 ***** 419 ***** 447 * 47 **** 420***** 448 * 48 ***** 421 ***** 449 * 51 ***** 422 ***** 450 * 63 *****423 ***** 451 * 64 ***** 424 **** 451 * 170 ***** 425 **** 452 * 176***** 426 **** 454 * 200 ***** 427 **** 455 * 207 **** 428 **** 456 *212 ***** 429 **** 456 * 218 ***** 430 **** 456 * 258 **** 431 ****457 * 307 **** 432 **** 458 * 315 ***** 433 **** 459 * 318 ***** 434 ***460 * 348 ***** 435 *** 461 * 350 ***** 436 *** 462 * 352 **** 437 **463 * 393 ***** 438 ** 464 * 411 ***** 439 ** 465 * 412 ***** 440 *

Without regard to whether a document cited herein was specifically andindividually indicated as being incorporated by reference, all documentsreferred to herein are incorporated by reference into the presentapplication for any and all purposes to the same extent as if eachindividual reference was fully set forth herein.

Having now fully described the subject matter of the claims, it will beunderstood by those having ordinary skill in the art that the same canbe performed within a wide range of equivalents without affecting thescope of the subject matter or embodiments described herein. It isintended that the appended claims be interpreted to include all suchequivalents.

What is claimed is:
 1. A compound of Formula (Ia11):

or a form thereof, wherein (when present), X is selected from O,NR_(5a), or a bond; A is selected from phenyl, thiophenyl, indazolyl,pyridinyl, pyrimidinyl or phenoxy, wherein phenyl and phenoxy are eachoptionally substituted with 1, 2 or 3 substituents each selected fromR_(1a), wherein thiophenyl, indazolyl, pyridinyl, pyrimidinyl are eachoptionally substituted with 1 or 2 substituents each selected fromR_(1a), R_(1a) is selected from halogen, hydroxyl, C₁₋₄alkyl,halo-C₁₋₄alkyl, amino, C₁₋₄alkoxy, or heteroaryl, wherein heteroaryl isa monocyclic, bicyclic, or polycyclic carbon atom ring structure radicalhaving one or more heteroatoms selected from O, S, and N, optionallysubstituted with 1 or 2 substituents each selected from R_(3a); whereinwhen A is phenyl, R_(1a) is not chloro or pyrazolyl; R_(3a) is selectedfrom nitro or C₁₋₄alkyl; R_(4a) is C₁₋₄alkyl; R_(5a) is hydrogen,C₁₋₄alkyl, or hydroxyl-C₁₋₄alkyl; wherein a form of the compound isselected from the group consisting of a salt, hydrate, solvate,isotopologue, racemate, enantiomer, diastereomer, stereoisomer, andtautomer form thereof.
 2. The compound of claim 1 wherein (whenpresent): R_(1a) is selected from fluoro, chloro, hydroxyl, methyl,difluoromethyl, amino, methoxy, 1H-pyrazolyl or 1H-imidazol-1-yl,wherein 1H-pyrazolyl is optionally substituted with 1 or 2 substituentseach selected from R_(3a); R_(3a) is selected from nitro or methyl; and,R_(4a) is methyl or ethyl; R_(5a) is hydrogen or methyl; wherein a formof the compound is selected from the group consisting of a salt,hydrate, solvate, isotopologue, racemate, enantiomer, diastereomer,stereoisomer, and tautomer form thereof.
 3. A compound, or form thereof,selected from the group consisting of:2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol,5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol,5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol,6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol,2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[4-(i-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol,2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol,N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole,3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine,3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol,6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine,3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol,6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-2-ol,N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine,N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine,3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine;wherein the form of the compound is selected from the group consistingof a salt, hydrate, solvate, isotopologue, racemate, enantiomer,diastereomer, stereoisomer, and tautomer form thereof.
 4. The compoundof claim 3, wherein the compound is a compound salt selected from thegroup consisting of:2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenolhydrochloride,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenolhydrochloride,5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenolhydrochloride,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenolhydrochloride,2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenoldihydrochloride,2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenoltrihydrochloride,5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenoltrihydrochloride,2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenoltrihydrochloride,2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenoltetrahydrochloride,2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenoltetrahydrochloride,6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminetetrahydrochloride,2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenolhydrochloride,6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride,3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinetrihydrochloride,2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenolhydrochloride,6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride,2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenoltrihydrochloride,3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinehydrochloride,2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenoltetrahydrochloride,3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinehydrochloride,3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinehydrochloride,6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminetrihydrochloride,3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinetrihydrochloride,3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-olhydrochloride,N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-aminehydrochloride,N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-aminehydrochloride,3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazinehydrochloride, and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminehydrochloride; wherein a form of the compound salt is selected from thegroup consisting of a hydrate, solvate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, and tautomer form thereof. 5.The compound of claim 1, wherein A is selected from thiophenyl,indazolyl, pyridinyl, pyrimidinyl and phenoxy.
 6. The compound of claim1, wherein when A is phenyl, R_(1a) is not hydroxyl.
 7. A compound ofFormula (Ia11):

or a form thereof, wherein (when present), X is selected from O,NR_(5a), or a bond; A is selected from phenyl, thiophenyl, indazolyl,pyridinyl, pyrimidinyl or phenoxy, wherein phenyl and phenoxy are eachoptionally substituted with 1, 2 or 3 substituents each selected fromR_(1a), wherein thiophenyl, indazolyl, pyridinyl, pyrimidinyl are eachoptionally substituted with 1 or 2 substituents each selected fromR_(1a), R_(1a) is selected from halogen, hydroxyl, C₁₋₄alkyl,halo-C₁₋₄alkyl, amino, C₁₋₄alkoxy, or heteroaryl, wherein heteroaryl isa monocyclic, bicyclic, or polycyclic carbon atom ring structure radicalhaving one or more heteroatoms selected from O, S, and N, optionallysubstituted with 1 or 2 substituents each selected from R_(3a); whereinwhen A is phenyl, R_(1a) is not hydroxyl; R_(3a) is selected from nitroor C₁₋₄alkyl; R_(4a) is C₁₋₄alkyl; R_(5a) is hydrogen, C₁₋₄alkyl, orhydroxyl-C₁₋₄alkyl; wherein a form of the compound is selected from thegroup consisting of a salt, hydrate, solvate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, and tautomer form thereof. 8.The compound of claim 7, wherein A is selected from thiophenyl,indazolyl, pyridinyl, pyrimidinyl and phenoxy.
 9. The compound of claim7, wherein (when present): R_(1a) is selected from fluoro, chloro,hydroxyl, methyl, difluoromethyl, amino, methoxy, 1H-pyrazolyl or1H-imidazol-1-yl, wherein 1H-pyrazolyl is optionally substituted with 1or 2 substituents each selected from R_(3a); R_(3a) is selected fromnitro or methyl; and, R_(4a) is methyl or ethyl; R_(5a) is hydrogen ormethyl; wherein a form of the compound is selected from the groupconsisting of a salt, hydrate, solvate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, and tautomer form thereof.
 10. Acompound selected from a compound Formula (Ia15) and Formula (Ia18):

or a form thereof, wherein (when present), X is selected from O,NR_(5a), or a bond; B is selected from 1H-pyrazolyl, piperidinyl,1,2,3,6-tetrahydropyridinyl, (1R,5S)-8-azabicyclo[3.2.1]octyl,8-azabicyclo[3.2.1]oct-2-enyl, 2,6-diazaspiro[3.4]octyl or2,7-diazaspiro[3.5]nonyl, each optionally substituted with 1 or 2substituents each selected from R_(4a); R_(1a) is selected from halogen,hydroxyl, C₁₋₄alkyl, halo-C₁₋₄alkyl, amino, C₁₋₄alkoxy, or heteroaryl,wherein heteroaryl is a monocyclic, bicyclic, or polycyclic carbon atomring structure radical having one or more heteroatoms selected from O,S, and N, optionally substituted with 1 or 2 substituents each selectedfrom R_(3a); wherein R_(1a) is not chloro or pyrazole; R_(3a) isselected from nitro or C₁₋₄alkyl; and, R_(4a) is C₁₋₄alkyl; R_(5a) ishydrogen, C₁₋₄alkyl, or hydroxyl-C₁₋₄alkyl; wherein a form of thecompound is selected from the group consisting of a salt, hydrate,solvate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer,and tautomer form thereof.
 11. The compound of claim 10, wherein (whenpresent): R_(1a) is selected from fluoro, hydroxyl, methyl,difluoromethyl, amino, methoxy, or 1H-imidazol-1-yl, R_(3a) is selectedfrom nitro or methyl; and, R_(4a) is methyl or ethyl; R_(5a) is hydrogenor methyl; wherein a form of the compound is selected from the groupconsisting of a salt, hydrate, solvate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, and tautomer form thereof. 12.The compound, or form thereof, of claim 3 selected from the groupconsisting of:2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol,5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol,6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol,2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol,3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[4-(i-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol,2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol,N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole,3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine,3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol,3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol,6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine,2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine,3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol,3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol,6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-2-ol,N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine,N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine,3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine,and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine;wherein the form of the compound is selected from the group consistingof a salt, hydrate, solvate, isotopologue, racemate, enantiomer,diastereomer, stereoisomer, and tautomer form thereof.